住院肿瘤患者药费分析以及妇科肿瘤相关危险因素的循证医学研究
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摘要
对于发达国家及发展中国家来说,癌症均是导致死亡的首要因素之一。在美国年龄小于85岁人群中,癌症已经超过心脏疾病成为首要致死因素。我们前期的研究发现随着中国的人群越来越多的采用西方的饮食习惯以及高压力的生活方式,许多慢性疾病包括癌症的发病率正在逐步上升。根据国家卫生统计部门统计,在城市癌症是首要的致死因素而在农村则位居第三。
癌症也给患者及他们的家庭乃至整个社会带来巨大的经济负担。许多发达国家已经开展了大量的关于癌症所带来的直接和间接医疗支出的研究。但是在中国这方面的研究还非常的缺乏。
癌症是基因环境相互作用,复杂的,多因素多步骤的结果。目前许多流行病学研究以及临床研究都对癌症的危险因素进行了探索,但是由于方法学等一些因素的不同导致结果往往有很大的差异,容易使人产生困惑或误解。在这种情况下,meta分析这种定量的文献分析方法可综合这些局部、分散的研究结果从而得到更加接近真实情况的综合分析结果。
第—部分:社会医疗保险对住院肿瘤患者药费的影响
1950到1980年间,城市地区的卫生保健制度主要包括两方面:一个是国家保险计划(government insurance scheme,GIS)又称为公费医疗,该计划主要涵盖了公共及政府部门的工作人员同时还包括了大学及学院的学生;另一个是劳动保险计划(labor insurancescheme,LIS),主要涵盖了在国家所有制以及集体所有制的企业工作的工人。但是,由于GIS和LIS的收益人在支付医疗费用方面只需要分担很少的费用,这样又导致中国医疗费用急剧的增加。
自1978年改革开放以来,中国原有的计划经济被市场经济所替代。为了在不减少医保覆盖率的基础上控制医疗卫生支出增长过快,中国进行了一系列的医疗保险制度的改革。1998年,中国政府作出了一项重大的政策决定,为城镇职工建立社会医疗保险(social healthinsurance,SHI)来替代之前的GIS和LIS,并实行社会统筹和个人帐户相结合的制度。这次改革主要目的就是使中国人民能更加有效及平等的获得医疗服务。中国政府还建立新的价格体系。这个价格体系里,绝大多数的服务项目的价格较低。但是,医院可以在药物以及检查费用上获取利润。
据我们所知,在中国医疗保险对于癌症患者药费的影响的研究还非常少。这次研究的主要目的就是评价SHI对癌症住院患者药物费用的影响以及探讨影响药物费用的因素。
1631名癌症患者纳入我们的研究中。癌症患者药费的中位数为RMB 8,069。在七种癌症中,药费最高的为食管癌(中位数=RMB11,028),最低的为乳腺癌(中位数=RMB 4,309)。SHI组患者用药费用(中位数=RMB 8,933)明显高于(P＜0.001)非SHI组(中位数=RMB 7,616)。根据癌症类型,在乳腺癌(P＜0.001),肺癌(P=0.018),肝癌(P=0.046),胰腺癌(P=0.040),食管癌(P=0.048)以及直肠结肠癌(P=0.004)中SHI组患者的药费均高于非SHI组。胃癌患者的药费在两组间未发现显著性差异(P=0.400)。
在根据年龄中位数(59岁)、性别和入院方式分层中SHI组的药费均高于非SHI组。根据LOS分层,SHI组在住院天数≤20(P＜0.001)和20-40(P=0.011)亚组中的用药费用高于非SHI组。但是在LOS≥41(P=0.568)亚组中未发现两组间存在显著性差异。
我们并没有发现SHI组和非SHI组患者在每天用药费用方面存在显著性差异(P=0.06)。经分层分析我们还发现只有在女性(P=0.016)、年轻者(P=0.023)以及住院天数在21-40亚组(P=0.003)中两组患者每天用药费用存在显著性差异。
多元线性回归分析结果显示年龄较大,SHI,长LOS,严重入院方式,女性均是引起药费增高的独立因素。在这些因素中,LOS的影响最大。回归分析结果还显示年龄是影响非SHI组患者药费高低最主要的因素,而LOS则是影响SHI组患者药费高低最主要的因素。
第二部分:饮茶与卵巢癌发病风险相关性的meta分析
茶叶是摘自茶树的顶端叶子,在世界范围内它是仅次于水的第二大饮料。目前许多实验性研究在探索茶对癌症的作用以及作用机制。迄今为止,大多数关于茶的研究关注的都是绿茶的效应和机制。绿茶主要含有儿茶素,有效的成分为EGCG(epigallocatechingallate),ECG(epicatechin gallate),EGC(epigallocatechin)和EC(epicatechin)儿茶素。在这些成分中,EGCG受到普遍关注,目前已发现它参与诱导凋亡,抑制细胞周期,抗氧化,吞噬自由基因,抑制肿瘤入侵和转移等过程。一些体外实验和动物实验发现红茶中富含的茶黄素以及茶玉红精也有抗癌活性,如可以调节H-ras,c-Myc,p53和Bcl-2等基因蛋白的表达水平从而诱导凋亡等。
最近的30多年里,关于饮茶与卵巢癌的发病风险相关性的流行病学研究有许多。但是,他们的结果并不完全一致的。而且据我们所知,到目前为止还没有一篇关于饮茶和卵巢癌发病风险的meta分析。因此,我们开展了这项meta分析,旨在进一步明确饮茶与卵巢癌发病风险的相关性。
两篇前瞻性研究和7篇病例对照研究纳入meta分析。合并的风险值没有表明饮茶与患卵巢癌的风险显著相关(RR=0.84,95%CI=0.66-1.07)。敏感性分析证实了合并结果的稳定性。前瞻性研究(RR=0.69,95%CI=0.45-1.06)以及病例对照研究的合并结果(RR=0.87,95%CI=0.67-1.13)均未发现饮茶与卵巢癌的风险显著相关。将来源于人群以及来源于医院的病例对照研究分开合并,我们并没有发现来源于人群(RR=1.06,95%CI=0.88-1.27)以及来源于医院(RR=0.73,95%CI=0.46-1.15)的病例对照研究的合并结果有明显的差异。
来自西方国家的8项研究的合并结果(RR=0.98,95%CI=0.84-1.15)以及来自西方国家的6项病例对照研究的合并结果都没发现饮茶与卵巢癌之间存在相关性(RR=1.04,95%CI=0.93-1.15)。西方国家的研究结果与来自中国的研究结果差异显著(P＜0.001)。
异质性检验结果表明9项研究间存在显著的异质性(P＜0.001),7项病例对照研究间也存在显著的异质性(P＜0.001)。但是,前瞻性研究间并没发现异质性(P=0.181)。敏感性分析表明异质性主要来源于Zhang等人在中国开展的这项研究。这篇文章排除后,8项研究(P=0.085)以及7项病例对照研究间(P=0.193)并没发现显著的异质性。直观的漏斗图以及Egger检验(P=0.191)中均未发现发表性偏见。
第三部分:激素替代治疗与卵巢癌发病风险相关性的meta分析
激素替代治疗(hormone replacement treatment,HRT)是用于替代女性体内一种或多种激素,以雌激素和孕激素常见。HRT原本用于缓解绝经期综合症,后来发现它还具有心脏保护以及减少骨质疏松引起的骨折等作用从而得到了广泛的应用。但是,许多研究发现HRT会增加癌症的发病率尤其增加女性生殖系统肿瘤的发生。现有研究已证实HRT使用者中乳腺癌及子宫内膜癌的发病率比未使用HRT人群要高,而且随着使用时间的递增风险增加。但是,HRT和卵巢癌发病风险的相关性还存在很大的争议,之前的meta分析结果差异也很大。meta分析结果大多都显示HRT与卵巢癌的发病风险无关或并不显著相关,而且这些分析的结果主要根据病例对照研究。近来,有许多大样本且随访时间较长的前瞻性研究探讨HRT和卵巢癌的相关性。而且其中有研究发现HRT可显著增加卵巢癌的发病风险。因此,我们开展了这项meta分析,旨在进一步明确HRT与卵巢癌发病风险的相关性。
8篇前瞻性文章合并结果显示使用HRT者患卵巢癌的风险增加了24%(95%CI=1.15-1.34),并且没有发现研究间存在异质性。此外,从直观的漏斗图以及Egger检验(P=0.496)中都没有发现发表性偏见。与未使用HRT者相比,现在使用HRT者患卵巢癌的风险显著上升(RR=1.28,95%CI=1.15-1.42)。合并结果显示曾经使用HRT与卵巢癌的发病风险未发现有显著相关性(RR=1.03,95%CI=0.95-1.13)。4篇前瞻性文章研究了雌激素替代治疗(estrogenreplacement therapy,ERT)以及雌孕激素替代治疗(estrogen plusprogestin replacement therapy,EPRT)与卵巢癌的关系。合并结果显示使用ERT者患卵巢癌的风险(RR=1.51,95%CI=1.21-1.88)要高于使用EPRT者(RR=1.24,95%CI=1.00-1.54)。
19篇病例对照研究合并结果显示与未使用HRT者相比,使用HRT者患卵巢癌的风险显著上升(RR=1.19,95%CI=1.02-1.40),但是研究间存在异质性。通过逐步排除的方法,我们发现Hartge et al和Tavani et al所做的这两个研究是引起异质性的主要来源。当这两个研究被排除,其余的17个研究间不存在异质性(P=0.120),合并的风险值为1.19(95%CI=1.07-1.32)。此外,从直观的漏斗图以及Egger检验(P=0.064)中都发现存在发表性偏见。19个病例对照研究中,8个是采用人群来源的病例对照研究的合并风险值为1.17(95%CI=1.01-1.35),11个是采用医院来源的病例对照研究的合并风险值为1.21(95%CI=0.92-1.60),没有达到统计学意义。6个病例对照文章研究了不同种类HRT与卵巢癌的关系。结果显示使用ERT者患卵巢癌的风险(RR=1.19,95%CI=1.01-1.40)要高于使用EPRT者(RR=1.01,95%CI=0.83-1.22)。
第四部分:吸烟与子宫内膜癌发病风险相关性的meta分析
关于子宫内膜癌致病的生物学机制,长期以来高雌激素水平合并不充足的孕激素这一假设得到了许多研究者的肯定。研究发现吸烟可通过其抗雌激素效应降低子宫内膜癌的患病风险。而吸烟的抗雌激素作用可能是通过增加2-羟基雌二醇的水平来实现的,因为2-羟基雌二醇能减少细胞增生降低子宫内膜癌的患病风险。此外,吸烟还能够增加循环中雄激素水平,而雄激素能够降低雌激素所引起的细胞增生从而起到保护作用。在过去三十年中,还有许多流行病学文章研究了吸烟和子宫内膜癌发病风险的关系,但是结果至今无人进行合并。所以我们开展了这项meta分析。
共10个前瞻性研究和24个病例对照研究纳入。前瞻性研究(RR=0.81,95%CI=0.74-0.88)以及病例对照研究的合并结果(RR=0.72,95%CI=0.66-0.79)均表明吸烟可显著降低患子宫内膜癌的风险。异质性检验结果发现前瞻性研究之间不存在异质性(P=0.338)而病例对照研究之间发现有异质性(P=0.021)。通过逐步排除的方法,我们发现Shields et al和Weiss et al所做的这两个研究是引起异质性的主要来源。当这两个研究被排除,其余22个病例对照研究间不存在异质性(P=0.180),合并的风险值为0.73(95%CI=0.67-0.82)。从直观的漏斗图以及Egger检验中均未发现前瞻性研究(P=0.460)以及病例对照研究(P=0.892)存在发表性偏见。
前瞻性研究的合并结果(RR=0.74,95%CI=0.64-0.84)以及病例对照研究的合并结果(RR=0.63,95%CI=0.55-0.72)均发现现在吸烟能显著降低患子宫内膜癌的风险。前瞻性研究的合并结果(RR=0.88,95%CI=0.78-0.99)以及病例对照研究的合并结果(RR=0.80,95%CI=0.72-0.88)显示曾经吸烟也可显著降低患子宫内膜癌的风险。
6项前瞻性研究以及6项病例对照研究纳入剂量-效应研究中。前瞻性研究的合并结果(RR=0.84,95%CI=0.71-0.99)以及病例对照研究的合并结果(RR=0.73,95%CI=0.60-0.89)都表明每天增加吸烟20只可显著降低患子宫内膜癌的风险。
一些文章还研究了吸烟对绝经前以及绝经后女性患子宫内膜癌的影响。合并结果发现吸烟可显著降低绝经后女性患子宫内膜癌的风险(RR=0.71,95%CI=0.65-0.78),但是对于绝经前女性未发现显著影响(RR=1.06,95%CI=0.88-1.28)。两者的风险值差异显著(P＜0.001)。一篇前瞻性文章以及5篇病例对照文章还研究了HRT使用对于吸烟和子宫内膜癌相关性的影响。根据这些文章所提供的结果,HRT使用者中吸烟者患子宫内膜癌的风险(RR=0.45,95%CI=0.29-0.70)比未使用HRT者中的吸烟者(RR=0.65,95%CI=0.51-0.84)要低。
第五部分:他莫昔芬与子宫内膜癌发病风险相关性的meta分析
他莫昔芬是一种非类固醇类合成雌激素的衍生物。从20世纪70年代开始,他莫昔芬就已经广泛用于乳腺癌的治疗同时还用于单边乳腺癌患者预防对侧乳房癌变。此外,初级预防研究还发现他莫昔芬可能能够作为高风险女性预防乳腺癌的药物。使用他莫昔芬最严重的不良反应就是它具有潜在的致癌性。在女性中,他莫昔芬最常导致的就是子宫内膜癌。一些研究中发现采用他莫昔芬治疗的女性患子宫内膜癌的几率显著增加。但是每个研究的结果之间差异很大,风险增加的幅度为两到七倍不等。据我们所知,到目前为止还没有一篇关于他莫昔芬和子宫内膜癌发病风险的meta分析。因此,我们开展了这项meta分析,旨在进一步明确他莫昔芬与子宫内膜癌发病风险的相关性。
14个随机对照研究(randomized controlled trials,RCTs)纳入meta分析。合并结果显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=3.0,95%CI=2.30-3.91),并且没有发现研究间存在异质性(P=0.74)。此外,直观的漏斗图以及Egger检验(P=0.21)中均未发现发表性偏见。将绝经后女性单独进行分析时我们发现他莫昔芬组患子宫内膜癌的风险显著的增加(RR=5.19,95%CI=2.58-10.47)。将预防的随机试验单独进行分析时我们发现他莫昔芬能显著增加患子宫内膜癌的风险(RR=2.61,95%CI=1.89-3.60)。
9个病例对照研究以及5个前瞻性研究也纳入meta分析。合并观察性文章的结果也显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=1.90,95%CI=1.40-2.47),但是研究间存在异质性(P＜0.001)。直观的漏斗图以及Egger检验(P=0.88)中都没有发现发表性偏见。分析结果发现在前瞻性研究(RR=2.18,95%CI=1.48-3.21)以及在病例对照研究(RR=1.36,95%CI=1.10-1.67)中他莫昔芬都能显著增加患子宫内膜癌的风险。异质性检验结果发现前瞻性研究间不存在异质性(P=0.71)而病例对照研究间发现有异质性(P＜0.001)。根据7篇文章所提供的结果进行不同使用时间对子宫内膜癌的影响的分析。服用他莫昔芬时间少于5年者患子宫内膜癌的风险呈中等程度的增加(RR=1.75,95%CI=1.29-2.37)。服用他莫昔芬5年以上者患子宫内膜癌的风险显著的增加(RR=5.86,95%CI=3.79-9.06)。
比较RCT以及观察性研究所得出的合并风险值发现两者之间存在显著性差异(P=0.02)。将RCT以及观察性研究的合并分析,结果显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=2.02,95%CI=1.82-2.25)。
Cancer is one of the leading causes of death in both developed and developing countries.In the United States,when deaths are aggregated by age,cancer has surpassed heart disease as the leading cause of death for those younger than age 85.As indicated previously by us,the populations in developing countries adopt Western diets and a high-stress lifestyle,the change of geographic distribution of many chronic diseases incidence has emerged,with a marked elevation in developing countries.According to national health statistics,cancer ranks as the first major cause of death among urban population and third among rural population in China.
Cancer is also associated with an immense economic burden on patients,families and society.Estimation of charges and costs for cancer has been performed in many developed countries.However,little has been known about the medical expenditures for cancer in China.
Cancer is considered to be a result of gene-environment interactions, which is a complex,multi-step and multi-factorial process.Many epidemiological studies and randomized controlled trials are aimed to assess the potential risk factors of cancer.However,due to the differences in the methodology,the results varied.Meta-analysis is a statistical technique for summarising,and reviewing the finding from independent studies to derive an overall estimate.By using meta-analysis,a wide variety of questions can be investigated.
PartⅠ:Social health insurance and drug expenditures among cancer inpatients in China
Between 1950 and 1980,in the urban areas the health care system in China traditionally comprised two major schemes:the government insurance scheme(GIS)covered workers in the public sector and government agencies as well as students in colleges and universities;and the labor insurance scheme(LIS)covered the workers in state-owned and collective-owned enterprises.However,GIS and LIS are third-party insurance,providing comprehensive benefits with minimal cost sharing to constrain beneficiaries,which contributed to China's rapid health care cost inflation.
Since 1978 when the economic reform was launched,the planned economy of China has been replaced by the market economy.Meanwhile, China announced series of health insurance system reform to control health care costs without reducing or dropping coverage.In 1998,the government made a major policy decision to establish a social health insurance(SHI)program for urban workers which replaced the existing GIS and LIS.The purposes of the reform were to ensure that the new SHI can be more efficient and more equitable in accessing health care. Furthermore,a new pricing structure was introduced.Most of the established services were priced below cost,while profits can be made from drugs and technology.
And to our knowledge,little is known about the association of health insurance coverage with drug expenditures among cancer patients in China.The present study is to assess the differences in drug expenditures among cancer inpatients according to SHI status and to explore the factors that influence drug costs.
One thousand six hundred and thirty one cancer inpatients were included in our study.The median drug cost was approximately RMB 8,069 per inpatient.Among these seven cancers,the median of drug cost was highest for esophageal cancer(median=RMB 11,028)and lowest for breast cancer(median=RMB 4,309).The drug cost for SHI inpatients (median=RMB 8,933)was significantly higher(P＜0.001)than that for non-SHI inpatients(median=RMB 7,616).Statistics tests for each type of cancer also showed that the differences were significant as regards breast (P＜0.001),lung(P=0.018),liver(P=0.046),pancreatic(P=0.040), esophageal(P=0.048)and colorectal(P=0.004)cancer,whereas the drug cost for gastric cancer showed no measurable difference(P=0.400).
We also performed stratified analyses by the median age of all patients (59 years),LOS,sex,type of admission.In statistical analyses stratified by age,sex and type of admission,the difference between SHI and non-SHI group were significant.When stratified by LOS,the significant differences according to SHI status remained in≤20(P＜0.001)and 20-40 LOS subgroups(P=0.011),but was lost in≥41 LOS subgroup(P=0.568).
We compared the drug cost per day between insured and uninsured inpatients.We did not observe a significant difference in drug cost per day between SHI and non-SHI patients(P=0.06).And the drug cost per day for female insured patients was significantly higher than that for female uninsured patients(P=0.016).The differences were also significant in younger patients(P=0.023)and in patients with 21-40 LOS subgroup(P=0.003).
The results of multiple linear regression analysis demonstrated that older age,SHI coverage,longer LOS,higher severity of admission,and female sex were associated positively and independently with higher drug costs.Among these factors,LOS made the largest contribution. Furthermore,the results of multiple linear regression analysis also demonstrated that age made the most effects on higher drug costs for non-SHI patients,while LOS was the most influential factor among SHI patients.
PartⅡ:The association of tea consumption with ovarian cancer risk:a meta-analysis
Tea,derived from the top leaves of the plant Camellia sinensis,is second only to water in terms of worldwide popularity as a beverage. Several laboratory studies found that tea may have anticancer activity. Most of tea researches to date have focused on the effect and mechanism of green tea.The main catechins,effective component in green tea,are epigallocatechin gallate(EGCG)and epicatechin gallate(ECG), epigallocatechin(EGC),and epicatechin(EC)catechins.In these components,EGCG has been the focus of a great deal of attention.It has been found to participate in induction of apoptosis and cell cycle arrest, antioxidation and scavenging the free radicals,inhibition of tumor invasion and metastasis.Extracts of black tea such as theaflavins and thearubigins also have been proved by some in vitro and animal studies to have anticarcinogenic properties,such as modulation protein expression of H-ras,c-Myc,p53,and Bcl-2 genes and induction of apoptosis.
Moreover,a number of epidemiologic studies also have been conducted to investigate the association of tea consumption with cancer risk including ovarian cancer risk.However,results of these studies were not entirely consistent.And to our knowledge,there is no meta-analysis concerning association between tea consumption and ovarian cancer risk.
Therefore,we undertook this meta-analysis to further clarify the association of tea consumption with ovarian cancer risk.
Two cohorts and seven case-control studies were included.The summary RR of all studies,did not show that tea consumption was associated with decreased risk of ovarian cancer(RR=0.84,95% CI=0.66-1.07).We also performed a sensitivity analysis which confirmed the stability of our results.The summary RRs neither from cohort studies(RR=0.69,95%CI=0.45-1.06)nor from all case-control studies(RR=0.87,95%CI=0.67-1.13)showed that tea intake was related to decreased ovarian cancer risk.When we separated the population-based case-control studies from their hospital-based case-control studies,we found no apparent difference between hospital-based case-control studies(RR=0.73,95%CI=0.46-1.15)and population-based case-control studies(RR=1.06,95%CI=0.88-1.27).
The summary RR of eight studies in all Western countries(RR=0.98, 95%CI=0.84=1.15)and the summary RR of six case-control studies in Western countries were not substantially altered(RR=1.04,95%CI= 0.93-1.15).The test for difference between study from China and studies from Western countries was statistically significant(P＜0.001).
There was statistically significant heterogeneity in results across the nine studies(P＜0.001)and seven case-control studies(P＜0.001). However,results from cohort studies alone did not reject the homogeneity hypothesis(P=0.181).The sensitivity analysis showed that the study in China as contributing most to the results and heterogeneity. When this study was excluded,the test of heterogeneity was not statistically significant in results across remain eight studies(P=0.085) and six case-control studies(P=0.193).In addition,no indication of publication bias was found from both visualization of the funnel plot and the Egger's test(P=0.191).
PartⅢ:The association of hormone replacement therapy with ovarian cancer risk:a meta-analysis
Hormone replacement treatment(HRT)is a form of treatment designed to replace one or more female hormones,commonly estrogen and progesterone.In addition to treating the menopausal symptoms such as hot flashes and sleep disorders,HRT gained popularity because it was thought to help reduce the risk of heart disease and bone fractures caused by osteoporosis.However,a number of studies have reported that HRT could increase the risk of cancer especially cancer of female reproductive organs.The available evidence indicated that the risk of breast or endometrial cancer was increased among HRT users,the risk increasing with increasing duration of use.However,knowledge about the relation between HRT use and ovarian cancer risk is less unequivocal and results of previous meta-analyses varied.There was either no suggestion of or a weak if any association between HRT and ovarian cancer and results were mainly restricted to finding of case-control studies.Several prospective cohort studies with large sample sizes and long term follow-up were published recently, providing evidence for an increased risk of ovarian cancer in HRT user. Therefore,we undertook this meta-analysis to further clarify the association of hormone replacement therapy with ovarian cancer risk.
Eight prospective studies met the inclusion criteria.The ever use of HRT was associated with a statistically significant 24%increased risk of ovarian cancer(95%CI=1.15-1.34);there was no significant heterogeneity among studies.In addition,no evidence of publication bias was observed with a nonsignificant Egger test(P=0.496).Compared with individuals who had never used HRT,those with current hormone use had a significant higher risk of ovarian cancer(RR=1.28,95% CI=1.15-1.42).Furthermore,Risk was higher among current users of more than 5 years(RR=1.47,95%CI=1.12-1.92)than among those of less than 5 years(RR=1.04,95%CI=0.91-1.20).However,for those with former HRT use,the association was not statistically significant (RR=1.03,95%CI=0.95-1.13).And we also did not find risk estimates significantly related to the duration of use for women who had former HRT use for less than 5 years(RR=1.00,95%CI=0.88-1.13),and for duration of 5 years or more(RR=1.10,95%CI=0.76-1.61).Four cohort studies addressed the association of ERT and EPRT with ovarian cancer, respectively.And a stronger association of ovarian cancer risk was noted in ERT users(RR=1.51,95%CI=1.21-1.88)than in EPRT users (RR=1.24,95%CI=1.00-1.54).
Nineteen case-control studies were included.Compared with women who had never used HRT,the pooled estimate of ovarian cancer was 1.19 (95%CI=1.02-1.40)for those who ever used HRT;but there was some indication of heterogeneity among studies.By using a stepwise process, we determined that most of the heterogeneity in the ever-use summary RR was accounted for two studies by Hartge et al.and by Tavani et al. When these two studies were excluded,the remaining studies were homogenous(P=0.120),and the summary estimate for ever use of HRT and ovarian cancer incidence was 1.19(95%CI=1.07-1.32).In additional, we did obtain evidence of publication bias as shown by a statistically significant P value of 0.064 from the Egger's test.The summary estimate was 1.17(95%CI=1.01-1.35)when we pooled eight case-control studies with population-based controls.When we combined 11 case-control studies with hospital-based controls,the association was not statistically significant(RR=1.21,95%CI=0.92-1.60).Summary RRs for the development of ovarian cancer with different type of hormone use were based on data abstract from six studies.And a stronger association of ovarian cancer risk was still noted in ERT users(RR=1.19,95%CI 1.01-1.40)than in EPRT users(RR=1.01,95%CI 0.83-1.22).
PartⅣ:The association of cigarette smoking with endometrial cancer risk:a meta-analysis
Endometrial cancer originates in the endometrial lining of the uterus. The major etiologic hypothesis for the development of endometrial cancer is exposure to high levels of estrogen in conjunction with inadequate progesterone.Several laboratory studies found that smoking could decrease the risk of endometrial cancer through its anti-estrogenic effect.The antiestrogenic effects of cigarette smoking might through increased level of 2-hydroxylation of estradiol which could decrease cellular proliferation and endometrial cancer risk.In addition,cigarette smoking could increase circulating androgens which might decrease estrogen-induced cellular proliferation in endometrial glands and protect against the development of endometrial cancer.During last three decades, many epidemiological studies have evaluated the association between cigarette smoking and endometrial cancer risk,and results of these studies have not yet been summarized.
Ten prospective and 24 case-control studies were included.We found that ever smoking was statistically significantly associated with reduced risk of endometrial cancer among prospective(RR=0.81,95% CI=0.74-0.88)and among case-control studies(RR=0.72,95% CI=0.66-0.79);there was statistically significant heterogeneity among case-control(P=0.021)but not among prospective studies(P=0.338).By using a stepwise process,we determined that most of the heterogeneity was accounted for two studies by Shields et al.and by Weiss et al.When these two studies were excluded,the summary estimate was unchanged (RR=0.73,95%CI=0.67-0.81),but a concomitant shift in heterogeneity was measured(from P=0.02 to P=0.180).Egger's test suggested no statistically significant asymmetry of the funnel plot for prospective (P=0.460)or cancer-control(P=0.892)studies.
The RR for current smoking were 0.74(95%CI=0.64-0.84)for prospective studies and 0.63(95%CI=0.55-0.72)for case-control studies. The RR for former smoking were 0.88(95%CI=0.78-0.99)for prospective studies and 0.80(95%CI=0.72-0.88)for case-control studies.
Six prospective and six case-control studies were included in this quantitative analysis.Overall,we found that an increment of 20 cigarettes per day was significantly inversely associated with endometrial cancer risk in prospective studies(RR=0.84,95%CI=0.71-0.99)or in case-control studies(RR=0.73,95%CI=0.60-0.89).
Several studies have examined this association according to menopausal status.Pooled results found that there was a statistically significant reduction in endometrial cancer risk for cigarette smoking among postmenopausal women(RR=0.71,95%CI=0.65-0.78)but not among premenopausal women(RR=1.06,95%CI=0.88-1.28).The difference between two estimates was statistically significant(P＜0.01). One prospective study and five case-control studies have examined this association according to HRT status.The risk reduction appeared to be stronger among HRT users(RR=0.45,95%CI=0.29-0.70)than among none users(RR=0.65,95%CI=0.51-0.84).
PartⅤ:The association of tamoxifen with endometrial cancer risk:a meta-analysis
Tamoxifen is a nonsteroidal triphenylethylene derivative that has been widely used to treat breast cancer since the early 1970s and that also reduces the risk of a contralateral malignancy in patients with unilateral breast cancer.Tamoxifen is being investigated in trials as a possible prophylactic agent in women at high risk of breast cancer.The most serious adverse effect of tamoxifen is its potential tumor-promoting activity.Treatment with tamoxifen has found to be associated with an increased risk of endometrial cancer,in accord with the selective uptake of tamoxifen by endometrial tissue,with its agonist effects on the endometrium,and with laboratory results.However,the magnitude of the increased risk varies substantially between studies.In these studies,the effect of tamoxifen on endometrial cancer has been reported to increase the incidence rate from two-fold to seven-fold.And to our knowledge, there is no meta-analysis concerning this association.Therefore,we undertook this meta-analysis.
Fourteen randomized controlled trials(RCTs)were included. Tamoxifen use was found to be statistically significantly associated with higher risk of endometrial cancer(RR=3.0,95%CI 2.30-3.91).The Cochran's Q test resulted in a P=0.74,indicating that the results of the RCT studies were homogeneous.The funnel plot had the expected funnel shape.The P values for the Egger test were P=0.21,suggesting a low probability of publication bias.When women who were postmenopausal or in treatment trials were considered separately,risk increases were greater(RR=5.19,95%CI 2.58-10.47).When women in risk reduction trials were considered separately,their risk increase was still statistically significant(RR=2.61,95%CI=1.89-3.60).
Nine case-control studies and five cohort studies were included. Tamoxifen use was modestly significantly related to the risk of endometrial cancer among observational studies(RR=1.90,95%CI 1.40-2.47).The Cochran's Q test resulted in a p＜0.01,indicating that the heterogeneity among the studies were high.The funnel plot also had the expected funnel shape and the P values for the Egger test were p=0.88. We found that the modest increase of endometrial cancer risk was statistically significant among the case-control studies(RR=2.18,95% CI=1.48-3.21)or among the cohort studies(RR=1.36,95% CI=1.10-1.67).We also conducted analysis based on data abstracted from seven studies to evaluate the association of endometrial cancer risk with different durations of tamoxifen use.The summary risk estimate for less than five years and were 1.75(95%CI=1.29-2.37).More than five years use of tamoxifen was found to be strongly associated with increased risk of endometrial cancer(RR=5.86,95%CI=3.79-9.06). And the difference between these two estimates was statistically significant(P＜0.01).
We compared the pooled RR estimates derived from the two separate analyses.The difference between estimates was statistically significant (P=0.02).In addition,we performed a combined analysis of RCTs and observational studies.Tamoxifen use was significantly related to the risk of endometrial cancer(RR=2.02,95%CI 1.82-2.25).
癌症也给患者及他们的家庭乃至整个社会带来巨大的经济负担。许多发达国家已经开展了大量的关于癌症所带来的直接和间接医疗支出的研究。但是在中国这方面的研究还非常的缺乏。
癌症是基因环境相互作用,复杂的,多因素多步骤的结果。目前许多流行病学研究以及临床研究都对癌症的危险因素进行了探索,但是由于方法学等一些因素的不同导致结果往往有很大的差异,容易使人产生困惑或误解。在这种情况下,meta分析这种定量的文献分析方法可综合这些局部、分散的研究结果从而得到更加接近真实情况的综合分析结果。
第—部分:社会医疗保险对住院肿瘤患者药费的影响
1950到1980年间,城市地区的卫生保健制度主要包括两方面:一个是国家保险计划(government insurance scheme,GIS)又称为公费医疗,该计划主要涵盖了公共及政府部门的工作人员同时还包括了大学及学院的学生;另一个是劳动保险计划(labor insurancescheme,LIS),主要涵盖了在国家所有制以及集体所有制的企业工作的工人。但是,由于GIS和LIS的收益人在支付医疗费用方面只需要分担很少的费用,这样又导致中国医疗费用急剧的增加。
自1978年改革开放以来,中国原有的计划经济被市场经济所替代。为了在不减少医保覆盖率的基础上控制医疗卫生支出增长过快,中国进行了一系列的医疗保险制度的改革。1998年,中国政府作出了一项重大的政策决定,为城镇职工建立社会医疗保险(social healthinsurance,SHI)来替代之前的GIS和LIS,并实行社会统筹和个人帐户相结合的制度。这次改革主要目的就是使中国人民能更加有效及平等的获得医疗服务。中国政府还建立新的价格体系。这个价格体系里,绝大多数的服务项目的价格较低。但是,医院可以在药物以及检查费用上获取利润。
据我们所知,在中国医疗保险对于癌症患者药费的影响的研究还非常少。这次研究的主要目的就是评价SHI对癌症住院患者药物费用的影响以及探讨影响药物费用的因素。
1631名癌症患者纳入我们的研究中。癌症患者药费的中位数为RMB 8,069。在七种癌症中,药费最高的为食管癌(中位数=RMB11,028),最低的为乳腺癌(中位数=RMB 4,309)。SHI组患者用药费用(中位数=RMB 8,933)明显高于(P＜0.001)非SHI组(中位数=RMB 7,616)。根据癌症类型,在乳腺癌(P＜0.001),肺癌(P=0.018),肝癌(P=0.046),胰腺癌(P=0.040),食管癌(P=0.048)以及直肠结肠癌(P=0.004)中SHI组患者的药费均高于非SHI组。胃癌患者的药费在两组间未发现显著性差异(P=0.400)。
在根据年龄中位数(59岁)、性别和入院方式分层中SHI组的药费均高于非SHI组。根据LOS分层,SHI组在住院天数≤20(P＜0.001)和20-40(P=0.011)亚组中的用药费用高于非SHI组。但是在LOS≥41(P=0.568)亚组中未发现两组间存在显著性差异。
我们并没有发现SHI组和非SHI组患者在每天用药费用方面存在显著性差异(P=0.06)。经分层分析我们还发现只有在女性(P=0.016)、年轻者(P=0.023)以及住院天数在21-40亚组(P=0.003)中两组患者每天用药费用存在显著性差异。
多元线性回归分析结果显示年龄较大,SHI,长LOS,严重入院方式,女性均是引起药费增高的独立因素。在这些因素中,LOS的影响最大。回归分析结果还显示年龄是影响非SHI组患者药费高低最主要的因素,而LOS则是影响SHI组患者药费高低最主要的因素。
第二部分:饮茶与卵巢癌发病风险相关性的meta分析
茶叶是摘自茶树的顶端叶子,在世界范围内它是仅次于水的第二大饮料。目前许多实验性研究在探索茶对癌症的作用以及作用机制。迄今为止,大多数关于茶的研究关注的都是绿茶的效应和机制。绿茶主要含有儿茶素,有效的成分为EGCG(epigallocatechingallate),ECG(epicatechin gallate),EGC(epigallocatechin)和EC(epicatechin)儿茶素。在这些成分中,EGCG受到普遍关注,目前已发现它参与诱导凋亡,抑制细胞周期,抗氧化,吞噬自由基因,抑制肿瘤入侵和转移等过程。一些体外实验和动物实验发现红茶中富含的茶黄素以及茶玉红精也有抗癌活性,如可以调节H-ras,c-Myc,p53和Bcl-2等基因蛋白的表达水平从而诱导凋亡等。
最近的30多年里,关于饮茶与卵巢癌的发病风险相关性的流行病学研究有许多。但是,他们的结果并不完全一致的。而且据我们所知,到目前为止还没有一篇关于饮茶和卵巢癌发病风险的meta分析。因此,我们开展了这项meta分析,旨在进一步明确饮茶与卵巢癌发病风险的相关性。
两篇前瞻性研究和7篇病例对照研究纳入meta分析。合并的风险值没有表明饮茶与患卵巢癌的风险显著相关(RR=0.84,95%CI=0.66-1.07)。敏感性分析证实了合并结果的稳定性。前瞻性研究(RR=0.69,95%CI=0.45-1.06)以及病例对照研究的合并结果(RR=0.87,95%CI=0.67-1.13)均未发现饮茶与卵巢癌的风险显著相关。将来源于人群以及来源于医院的病例对照研究分开合并,我们并没有发现来源于人群(RR=1.06,95%CI=0.88-1.27)以及来源于医院(RR=0.73,95%CI=0.46-1.15)的病例对照研究的合并结果有明显的差异。
来自西方国家的8项研究的合并结果(RR=0.98,95%CI=0.84-1.15)以及来自西方国家的6项病例对照研究的合并结果都没发现饮茶与卵巢癌之间存在相关性(RR=1.04,95%CI=0.93-1.15)。西方国家的研究结果与来自中国的研究结果差异显著(P＜0.001)。
异质性检验结果表明9项研究间存在显著的异质性(P＜0.001),7项病例对照研究间也存在显著的异质性(P＜0.001)。但是,前瞻性研究间并没发现异质性(P=0.181)。敏感性分析表明异质性主要来源于Zhang等人在中国开展的这项研究。这篇文章排除后,8项研究(P=0.085)以及7项病例对照研究间(P=0.193)并没发现显著的异质性。直观的漏斗图以及Egger检验(P=0.191)中均未发现发表性偏见。
第三部分:激素替代治疗与卵巢癌发病风险相关性的meta分析
激素替代治疗(hormone replacement treatment,HRT)是用于替代女性体内一种或多种激素,以雌激素和孕激素常见。HRT原本用于缓解绝经期综合症,后来发现它还具有心脏保护以及减少骨质疏松引起的骨折等作用从而得到了广泛的应用。但是,许多研究发现HRT会增加癌症的发病率尤其增加女性生殖系统肿瘤的发生。现有研究已证实HRT使用者中乳腺癌及子宫内膜癌的发病率比未使用HRT人群要高,而且随着使用时间的递增风险增加。但是,HRT和卵巢癌发病风险的相关性还存在很大的争议,之前的meta分析结果差异也很大。meta分析结果大多都显示HRT与卵巢癌的发病风险无关或并不显著相关,而且这些分析的结果主要根据病例对照研究。近来,有许多大样本且随访时间较长的前瞻性研究探讨HRT和卵巢癌的相关性。而且其中有研究发现HRT可显著增加卵巢癌的发病风险。因此,我们开展了这项meta分析,旨在进一步明确HRT与卵巢癌发病风险的相关性。
8篇前瞻性文章合并结果显示使用HRT者患卵巢癌的风险增加了24%(95%CI=1.15-1.34),并且没有发现研究间存在异质性。此外,从直观的漏斗图以及Egger检验(P=0.496)中都没有发现发表性偏见。与未使用HRT者相比,现在使用HRT者患卵巢癌的风险显著上升(RR=1.28,95%CI=1.15-1.42)。合并结果显示曾经使用HRT与卵巢癌的发病风险未发现有显著相关性(RR=1.03,95%CI=0.95-1.13)。4篇前瞻性文章研究了雌激素替代治疗(estrogenreplacement therapy,ERT)以及雌孕激素替代治疗(estrogen plusprogestin replacement therapy,EPRT)与卵巢癌的关系。合并结果显示使用ERT者患卵巢癌的风险(RR=1.51,95%CI=1.21-1.88)要高于使用EPRT者(RR=1.24,95%CI=1.00-1.54)。
19篇病例对照研究合并结果显示与未使用HRT者相比,使用HRT者患卵巢癌的风险显著上升(RR=1.19,95%CI=1.02-1.40),但是研究间存在异质性。通过逐步排除的方法,我们发现Hartge et al和Tavani et al所做的这两个研究是引起异质性的主要来源。当这两个研究被排除,其余的17个研究间不存在异质性(P=0.120),合并的风险值为1.19(95%CI=1.07-1.32)。此外,从直观的漏斗图以及Egger检验(P=0.064)中都发现存在发表性偏见。19个病例对照研究中,8个是采用人群来源的病例对照研究的合并风险值为1.17(95%CI=1.01-1.35),11个是采用医院来源的病例对照研究的合并风险值为1.21(95%CI=0.92-1.60),没有达到统计学意义。6个病例对照文章研究了不同种类HRT与卵巢癌的关系。结果显示使用ERT者患卵巢癌的风险(RR=1.19,95%CI=1.01-1.40)要高于使用EPRT者(RR=1.01,95%CI=0.83-1.22)。
第四部分:吸烟与子宫内膜癌发病风险相关性的meta分析
关于子宫内膜癌致病的生物学机制,长期以来高雌激素水平合并不充足的孕激素这一假设得到了许多研究者的肯定。研究发现吸烟可通过其抗雌激素效应降低子宫内膜癌的患病风险。而吸烟的抗雌激素作用可能是通过增加2-羟基雌二醇的水平来实现的,因为2-羟基雌二醇能减少细胞增生降低子宫内膜癌的患病风险。此外,吸烟还能够增加循环中雄激素水平,而雄激素能够降低雌激素所引起的细胞增生从而起到保护作用。在过去三十年中,还有许多流行病学文章研究了吸烟和子宫内膜癌发病风险的关系,但是结果至今无人进行合并。所以我们开展了这项meta分析。
共10个前瞻性研究和24个病例对照研究纳入。前瞻性研究(RR=0.81,95%CI=0.74-0.88)以及病例对照研究的合并结果(RR=0.72,95%CI=0.66-0.79)均表明吸烟可显著降低患子宫内膜癌的风险。异质性检验结果发现前瞻性研究之间不存在异质性(P=0.338)而病例对照研究之间发现有异质性(P=0.021)。通过逐步排除的方法,我们发现Shields et al和Weiss et al所做的这两个研究是引起异质性的主要来源。当这两个研究被排除,其余22个病例对照研究间不存在异质性(P=0.180),合并的风险值为0.73(95%CI=0.67-0.82)。从直观的漏斗图以及Egger检验中均未发现前瞻性研究(P=0.460)以及病例对照研究(P=0.892)存在发表性偏见。
前瞻性研究的合并结果(RR=0.74,95%CI=0.64-0.84)以及病例对照研究的合并结果(RR=0.63,95%CI=0.55-0.72)均发现现在吸烟能显著降低患子宫内膜癌的风险。前瞻性研究的合并结果(RR=0.88,95%CI=0.78-0.99)以及病例对照研究的合并结果(RR=0.80,95%CI=0.72-0.88)显示曾经吸烟也可显著降低患子宫内膜癌的风险。
6项前瞻性研究以及6项病例对照研究纳入剂量-效应研究中。前瞻性研究的合并结果(RR=0.84,95%CI=0.71-0.99)以及病例对照研究的合并结果(RR=0.73,95%CI=0.60-0.89)都表明每天增加吸烟20只可显著降低患子宫内膜癌的风险。
一些文章还研究了吸烟对绝经前以及绝经后女性患子宫内膜癌的影响。合并结果发现吸烟可显著降低绝经后女性患子宫内膜癌的风险(RR=0.71,95%CI=0.65-0.78),但是对于绝经前女性未发现显著影响(RR=1.06,95%CI=0.88-1.28)。两者的风险值差异显著(P＜0.001)。一篇前瞻性文章以及5篇病例对照文章还研究了HRT使用对于吸烟和子宫内膜癌相关性的影响。根据这些文章所提供的结果,HRT使用者中吸烟者患子宫内膜癌的风险(RR=0.45,95%CI=0.29-0.70)比未使用HRT者中的吸烟者(RR=0.65,95%CI=0.51-0.84)要低。
第五部分:他莫昔芬与子宫内膜癌发病风险相关性的meta分析
他莫昔芬是一种非类固醇类合成雌激素的衍生物。从20世纪70年代开始,他莫昔芬就已经广泛用于乳腺癌的治疗同时还用于单边乳腺癌患者预防对侧乳房癌变。此外,初级预防研究还发现他莫昔芬可能能够作为高风险女性预防乳腺癌的药物。使用他莫昔芬最严重的不良反应就是它具有潜在的致癌性。在女性中,他莫昔芬最常导致的就是子宫内膜癌。一些研究中发现采用他莫昔芬治疗的女性患子宫内膜癌的几率显著增加。但是每个研究的结果之间差异很大,风险增加的幅度为两到七倍不等。据我们所知,到目前为止还没有一篇关于他莫昔芬和子宫内膜癌发病风险的meta分析。因此,我们开展了这项meta分析,旨在进一步明确他莫昔芬与子宫内膜癌发病风险的相关性。
14个随机对照研究(randomized controlled trials,RCTs)纳入meta分析。合并结果显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=3.0,95%CI=2.30-3.91),并且没有发现研究间存在异质性(P=0.74)。此外,直观的漏斗图以及Egger检验(P=0.21)中均未发现发表性偏见。将绝经后女性单独进行分析时我们发现他莫昔芬组患子宫内膜癌的风险显著的增加(RR=5.19,95%CI=2.58-10.47)。将预防的随机试验单独进行分析时我们发现他莫昔芬能显著增加患子宫内膜癌的风险(RR=2.61,95%CI=1.89-3.60)。
9个病例对照研究以及5个前瞻性研究也纳入meta分析。合并观察性文章的结果也显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=1.90,95%CI=1.40-2.47),但是研究间存在异质性(P＜0.001)。直观的漏斗图以及Egger检验(P=0.88)中都没有发现发表性偏见。分析结果发现在前瞻性研究(RR=2.18,95%CI=1.48-3.21)以及在病例对照研究(RR=1.36,95%CI=1.10-1.67)中他莫昔芬都能显著增加患子宫内膜癌的风险。异质性检验结果发现前瞻性研究间不存在异质性(P=0.71)而病例对照研究间发现有异质性(P＜0.001)。根据7篇文章所提供的结果进行不同使用时间对子宫内膜癌的影响的分析。服用他莫昔芬时间少于5年者患子宫内膜癌的风险呈中等程度的增加(RR=1.75,95%CI=1.29-2.37)。服用他莫昔芬5年以上者患子宫内膜癌的风险显著的增加(RR=5.86,95%CI=3.79-9.06)。
比较RCT以及观察性研究所得出的合并风险值发现两者之间存在显著性差异(P=0.02)。将RCT以及观察性研究的合并分析,结果显示他莫昔芬可显著增加患子宫内膜癌的风险(RR=2.02,95%CI=1.82-2.25)。
Cancer is one of the leading causes of death in both developed and developing countries.In the United States,when deaths are aggregated by age,cancer has surpassed heart disease as the leading cause of death for those younger than age 85.As indicated previously by us,the populations in developing countries adopt Western diets and a high-stress lifestyle,the change of geographic distribution of many chronic diseases incidence has emerged,with a marked elevation in developing countries.According to national health statistics,cancer ranks as the first major cause of death among urban population and third among rural population in China.
Cancer is also associated with an immense economic burden on patients,families and society.Estimation of charges and costs for cancer has been performed in many developed countries.However,little has been known about the medical expenditures for cancer in China.
Cancer is considered to be a result of gene-environment interactions, which is a complex,multi-step and multi-factorial process.Many epidemiological studies and randomized controlled trials are aimed to assess the potential risk factors of cancer.However,due to the differences in the methodology,the results varied.Meta-analysis is a statistical technique for summarising,and reviewing the finding from independent studies to derive an overall estimate.By using meta-analysis,a wide variety of questions can be investigated.
PartⅠ:Social health insurance and drug expenditures among cancer inpatients in China
Between 1950 and 1980,in the urban areas the health care system in China traditionally comprised two major schemes:the government insurance scheme(GIS)covered workers in the public sector and government agencies as well as students in colleges and universities;and the labor insurance scheme(LIS)covered the workers in state-owned and collective-owned enterprises.However,GIS and LIS are third-party insurance,providing comprehensive benefits with minimal cost sharing to constrain beneficiaries,which contributed to China's rapid health care cost inflation.
Since 1978 when the economic reform was launched,the planned economy of China has been replaced by the market economy.Meanwhile, China announced series of health insurance system reform to control health care costs without reducing or dropping coverage.In 1998,the government made a major policy decision to establish a social health insurance(SHI)program for urban workers which replaced the existing GIS and LIS.The purposes of the reform were to ensure that the new SHI can be more efficient and more equitable in accessing health care. Furthermore,a new pricing structure was introduced.Most of the established services were priced below cost,while profits can be made from drugs and technology.
And to our knowledge,little is known about the association of health insurance coverage with drug expenditures among cancer patients in China.The present study is to assess the differences in drug expenditures among cancer inpatients according to SHI status and to explore the factors that influence drug costs.
One thousand six hundred and thirty one cancer inpatients were included in our study.The median drug cost was approximately RMB 8,069 per inpatient.Among these seven cancers,the median of drug cost was highest for esophageal cancer(median=RMB 11,028)and lowest for breast cancer(median=RMB 4,309).The drug cost for SHI inpatients (median=RMB 8,933)was significantly higher(P＜0.001)than that for non-SHI inpatients(median=RMB 7,616).Statistics tests for each type of cancer also showed that the differences were significant as regards breast (P＜0.001),lung(P=0.018),liver(P=0.046),pancreatic(P=0.040), esophageal(P=0.048)and colorectal(P=0.004)cancer,whereas the drug cost for gastric cancer showed no measurable difference(P=0.400).
We also performed stratified analyses by the median age of all patients (59 years),LOS,sex,type of admission.In statistical analyses stratified by age,sex and type of admission,the difference between SHI and non-SHI group were significant.When stratified by LOS,the significant differences according to SHI status remained in≤20(P＜0.001)and 20-40 LOS subgroups(P=0.011),but was lost in≥41 LOS subgroup(P=0.568).
We compared the drug cost per day between insured and uninsured inpatients.We did not observe a significant difference in drug cost per day between SHI and non-SHI patients(P=0.06).And the drug cost per day for female insured patients was significantly higher than that for female uninsured patients(P=0.016).The differences were also significant in younger patients(P=0.023)and in patients with 21-40 LOS subgroup(P=0.003).
The results of multiple linear regression analysis demonstrated that older age,SHI coverage,longer LOS,higher severity of admission,and female sex were associated positively and independently with higher drug costs.Among these factors,LOS made the largest contribution. Furthermore,the results of multiple linear regression analysis also demonstrated that age made the most effects on higher drug costs for non-SHI patients,while LOS was the most influential factor among SHI patients.
PartⅡ:The association of tea consumption with ovarian cancer risk:a meta-analysis
Tea,derived from the top leaves of the plant Camellia sinensis,is second only to water in terms of worldwide popularity as a beverage. Several laboratory studies found that tea may have anticancer activity. Most of tea researches to date have focused on the effect and mechanism of green tea.The main catechins,effective component in green tea,are epigallocatechin gallate(EGCG)and epicatechin gallate(ECG), epigallocatechin(EGC),and epicatechin(EC)catechins.In these components,EGCG has been the focus of a great deal of attention.It has been found to participate in induction of apoptosis and cell cycle arrest, antioxidation and scavenging the free radicals,inhibition of tumor invasion and metastasis.Extracts of black tea such as theaflavins and thearubigins also have been proved by some in vitro and animal studies to have anticarcinogenic properties,such as modulation protein expression of H-ras,c-Myc,p53,and Bcl-2 genes and induction of apoptosis.
Moreover,a number of epidemiologic studies also have been conducted to investigate the association of tea consumption with cancer risk including ovarian cancer risk.However,results of these studies were not entirely consistent.And to our knowledge,there is no meta-analysis concerning association between tea consumption and ovarian cancer risk.
Therefore,we undertook this meta-analysis to further clarify the association of tea consumption with ovarian cancer risk.
Two cohorts and seven case-control studies were included.The summary RR of all studies,did not show that tea consumption was associated with decreased risk of ovarian cancer(RR=0.84,95% CI=0.66-1.07).We also performed a sensitivity analysis which confirmed the stability of our results.The summary RRs neither from cohort studies(RR=0.69,95%CI=0.45-1.06)nor from all case-control studies(RR=0.87,95%CI=0.67-1.13)showed that tea intake was related to decreased ovarian cancer risk.When we separated the population-based case-control studies from their hospital-based case-control studies,we found no apparent difference between hospital-based case-control studies(RR=0.73,95%CI=0.46-1.15)and population-based case-control studies(RR=1.06,95%CI=0.88-1.27).
The summary RR of eight studies in all Western countries(RR=0.98, 95%CI=0.84=1.15)and the summary RR of six case-control studies in Western countries were not substantially altered(RR=1.04,95%CI= 0.93-1.15).The test for difference between study from China and studies from Western countries was statistically significant(P＜0.001).
There was statistically significant heterogeneity in results across the nine studies(P＜0.001)and seven case-control studies(P＜0.001). However,results from cohort studies alone did not reject the homogeneity hypothesis(P=0.181).The sensitivity analysis showed that the study in China as contributing most to the results and heterogeneity. When this study was excluded,the test of heterogeneity was not statistically significant in results across remain eight studies(P=0.085) and six case-control studies(P=0.193).In addition,no indication of publication bias was found from both visualization of the funnel plot and the Egger's test(P=0.191).
PartⅢ:The association of hormone replacement therapy with ovarian cancer risk:a meta-analysis
Hormone replacement treatment(HRT)is a form of treatment designed to replace one or more female hormones,commonly estrogen and progesterone.In addition to treating the menopausal symptoms such as hot flashes and sleep disorders,HRT gained popularity because it was thought to help reduce the risk of heart disease and bone fractures caused by osteoporosis.However,a number of studies have reported that HRT could increase the risk of cancer especially cancer of female reproductive organs.The available evidence indicated that the risk of breast or endometrial cancer was increased among HRT users,the risk increasing with increasing duration of use.However,knowledge about the relation between HRT use and ovarian cancer risk is less unequivocal and results of previous meta-analyses varied.There was either no suggestion of or a weak if any association between HRT and ovarian cancer and results were mainly restricted to finding of case-control studies.Several prospective cohort studies with large sample sizes and long term follow-up were published recently, providing evidence for an increased risk of ovarian cancer in HRT user. Therefore,we undertook this meta-analysis to further clarify the association of hormone replacement therapy with ovarian cancer risk.
Eight prospective studies met the inclusion criteria.The ever use of HRT was associated with a statistically significant 24%increased risk of ovarian cancer(95%CI=1.15-1.34);there was no significant heterogeneity among studies.In addition,no evidence of publication bias was observed with a nonsignificant Egger test(P=0.496).Compared with individuals who had never used HRT,those with current hormone use had a significant higher risk of ovarian cancer(RR=1.28,95% CI=1.15-1.42).Furthermore,Risk was higher among current users of more than 5 years(RR=1.47,95%CI=1.12-1.92)than among those of less than 5 years(RR=1.04,95%CI=0.91-1.20).However,for those with former HRT use,the association was not statistically significant (RR=1.03,95%CI=0.95-1.13).And we also did not find risk estimates significantly related to the duration of use for women who had former HRT use for less than 5 years(RR=1.00,95%CI=0.88-1.13),and for duration of 5 years or more(RR=1.10,95%CI=0.76-1.61).Four cohort studies addressed the association of ERT and EPRT with ovarian cancer, respectively.And a stronger association of ovarian cancer risk was noted in ERT users(RR=1.51,95%CI=1.21-1.88)than in EPRT users (RR=1.24,95%CI=1.00-1.54).
Nineteen case-control studies were included.Compared with women who had never used HRT,the pooled estimate of ovarian cancer was 1.19 (95%CI=1.02-1.40)for those who ever used HRT;but there was some indication of heterogeneity among studies.By using a stepwise process, we determined that most of the heterogeneity in the ever-use summary RR was accounted for two studies by Hartge et al.and by Tavani et al. When these two studies were excluded,the remaining studies were homogenous(P=0.120),and the summary estimate for ever use of HRT and ovarian cancer incidence was 1.19(95%CI=1.07-1.32).In additional, we did obtain evidence of publication bias as shown by a statistically significant P value of 0.064 from the Egger's test.The summary estimate was 1.17(95%CI=1.01-1.35)when we pooled eight case-control studies with population-based controls.When we combined 11 case-control studies with hospital-based controls,the association was not statistically significant(RR=1.21,95%CI=0.92-1.60).Summary RRs for the development of ovarian cancer with different type of hormone use were based on data abstract from six studies.And a stronger association of ovarian cancer risk was still noted in ERT users(RR=1.19,95%CI 1.01-1.40)than in EPRT users(RR=1.01,95%CI 0.83-1.22).
PartⅣ:The association of cigarette smoking with endometrial cancer risk:a meta-analysis
Endometrial cancer originates in the endometrial lining of the uterus. The major etiologic hypothesis for the development of endometrial cancer is exposure to high levels of estrogen in conjunction with inadequate progesterone.Several laboratory studies found that smoking could decrease the risk of endometrial cancer through its anti-estrogenic effect.The antiestrogenic effects of cigarette smoking might through increased level of 2-hydroxylation of estradiol which could decrease cellular proliferation and endometrial cancer risk.In addition,cigarette smoking could increase circulating androgens which might decrease estrogen-induced cellular proliferation in endometrial glands and protect against the development of endometrial cancer.During last three decades, many epidemiological studies have evaluated the association between cigarette smoking and endometrial cancer risk,and results of these studies have not yet been summarized.
Ten prospective and 24 case-control studies were included.We found that ever smoking was statistically significantly associated with reduced risk of endometrial cancer among prospective(RR=0.81,95% CI=0.74-0.88)and among case-control studies(RR=0.72,95% CI=0.66-0.79);there was statistically significant heterogeneity among case-control(P=0.021)but not among prospective studies(P=0.338).By using a stepwise process,we determined that most of the heterogeneity was accounted for two studies by Shields et al.and by Weiss et al.When these two studies were excluded,the summary estimate was unchanged (RR=0.73,95%CI=0.67-0.81),but a concomitant shift in heterogeneity was measured(from P=0.02 to P=0.180).Egger's test suggested no statistically significant asymmetry of the funnel plot for prospective (P=0.460)or cancer-control(P=0.892)studies.
The RR for current smoking were 0.74(95%CI=0.64-0.84)for prospective studies and 0.63(95%CI=0.55-0.72)for case-control studies. The RR for former smoking were 0.88(95%CI=0.78-0.99)for prospective studies and 0.80(95%CI=0.72-0.88)for case-control studies.
Six prospective and six case-control studies were included in this quantitative analysis.Overall,we found that an increment of 20 cigarettes per day was significantly inversely associated with endometrial cancer risk in prospective studies(RR=0.84,95%CI=0.71-0.99)or in case-control studies(RR=0.73,95%CI=0.60-0.89).
Several studies have examined this association according to menopausal status.Pooled results found that there was a statistically significant reduction in endometrial cancer risk for cigarette smoking among postmenopausal women(RR=0.71,95%CI=0.65-0.78)but not among premenopausal women(RR=1.06,95%CI=0.88-1.28).The difference between two estimates was statistically significant(P＜0.01). One prospective study and five case-control studies have examined this association according to HRT status.The risk reduction appeared to be stronger among HRT users(RR=0.45,95%CI=0.29-0.70)than among none users(RR=0.65,95%CI=0.51-0.84).
PartⅤ:The association of tamoxifen with endometrial cancer risk:a meta-analysis
Tamoxifen is a nonsteroidal triphenylethylene derivative that has been widely used to treat breast cancer since the early 1970s and that also reduces the risk of a contralateral malignancy in patients with unilateral breast cancer.Tamoxifen is being investigated in trials as a possible prophylactic agent in women at high risk of breast cancer.The most serious adverse effect of tamoxifen is its potential tumor-promoting activity.Treatment with tamoxifen has found to be associated with an increased risk of endometrial cancer,in accord with the selective uptake of tamoxifen by endometrial tissue,with its agonist effects on the endometrium,and with laboratory results.However,the magnitude of the increased risk varies substantially between studies.In these studies,the effect of tamoxifen on endometrial cancer has been reported to increase the incidence rate from two-fold to seven-fold.And to our knowledge, there is no meta-analysis concerning this association.Therefore,we undertook this meta-analysis.
Fourteen randomized controlled trials(RCTs)were included. Tamoxifen use was found to be statistically significantly associated with higher risk of endometrial cancer(RR=3.0,95%CI 2.30-3.91).The Cochran's Q test resulted in a P=0.74,indicating that the results of the RCT studies were homogeneous.The funnel plot had the expected funnel shape.The P values for the Egger test were P=0.21,suggesting a low probability of publication bias.When women who were postmenopausal or in treatment trials were considered separately,risk increases were greater(RR=5.19,95%CI 2.58-10.47).When women in risk reduction trials were considered separately,their risk increase was still statistically significant(RR=2.61,95%CI=1.89-3.60).
Nine case-control studies and five cohort studies were included. Tamoxifen use was modestly significantly related to the risk of endometrial cancer among observational studies(RR=1.90,95%CI 1.40-2.47).The Cochran's Q test resulted in a p＜0.01,indicating that the heterogeneity among the studies were high.The funnel plot also had the expected funnel shape and the P values for the Egger test were p=0.88. We found that the modest increase of endometrial cancer risk was statistically significant among the case-control studies(RR=2.18,95% CI=1.48-3.21)or among the cohort studies(RR=1.36,95% CI=1.10-1.67).We also conducted analysis based on data abstracted from seven studies to evaluate the association of endometrial cancer risk with different durations of tamoxifen use.The summary risk estimate for less than five years and were 1.75(95%CI=1.29-2.37).More than five years use of tamoxifen was found to be strongly associated with increased risk of endometrial cancer(RR=5.86,95%CI=3.79-9.06). And the difference between these two estimates was statistically significant(P＜0.01).
We compared the pooled RR estimates derived from the two separate analyses.The difference between estimates was statistically significant (P=0.02).In addition,we performed a combined analysis of RCTs and observational studies.Tamoxifen use was significantly related to the risk of endometrial cancer(RR=2.02,95%CI 1.82-2.25).
引文
[1] Brown ML, Lipscomb J, Snyder C. The burden of illness of cancer: economic cost and quality of life. Annu Rev Public Health 2001;22:91-113.
[2] Chang S, Long SR, Kutikova L, et al. Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000. J Clin Oncol 2004;22:3524-30.
[3] Zhu H, Yang L, Zhou B, et al. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis 2006;27:2491-6.
[4] Wang B. Major causes of death in China. N Engl J Med 2006;354:874-5.
[5] Wang B, Zhu H, Sun H, et al. Plasma 8-isoprostane concentrations in patients with age-related cataracts. Clin Chem 2005;51:1541-4.
[6] Wang B, Pan J, Wang L, et al. Associations of plasma 8-isoprostane levels with the presence and extent of coronary stenosis in patients with coronary artery disease. Atherosclerosis 2006;184:425-30.
[7] Ho LS. Market reforms and China's health care system. Soc Sci Med 1995;41:1065-72.
[8] Hsiao WC. The Chinese health care system: lessons for other nations. Soc Sci Med 1995;41:1047-55.
[9] Liu Y. Reforming China's urban health insurance system. Health Policy 2002;60:133-50.
[10] Liu Y, Hsiao WC, Eggleston K. Equity in health and health care: the Chinese experience. Soc Sci Med 1999;49:1349-56.
[11] Meng Q, Cheng G, Silver L, et al. The impact of China's retail drug price control policy on hospital expenditures: a case study in two Shandong hospitals. Health Policy Plan 2005;20:185-96.
[12] Gao J, Tang S, Tolhurst R, et al. Changing access to health services in urban China: implications for equity. Health Policy Plan 2001;16:302-12.
[13] Wu M, Xin Y, Wang H, et al. Private and public cross-subsidization: financing Beijing's health-insurance reform. Health Policy 2005;72:41-52
[14] Eggleston K, Yip W. Hospital competition under regulated prices: application to urban health sector reforms in China. Int J Health Care Finance Econ 2004;4:343-68.
[15] Doherty J, Kamae I, Lee KK, et al. What is next for pharmacoeconomics and outcomes research in Asia? Value Health 2004;7:118-32.
[16] Danis M, Linde-Zwirble WT, Astor A, et al. How does lack of insurance affect use of intensive care? A population-based study. Crit Care Med 2006;34:2043-8.
[17] Xu X, Patel DA, Vahratian A, et al. Insurance coverage and health care use among near-elderly women. Womens Health Issues 2006;16:139-48.
[18] Markovitz BP, Andresen EM. Lack of insurance coverage and urgent care use for asthma: a retrospective cohort study. BMC Public Health 2006;6:14.
[19] Boddiger D. Lack of insurance hinders Americans' diabetes care. Lancet 2006;368:15-6.
[20] Dong H, Bogg L, Wang K, et al. A description of outpatient drug use in rural China: evidence of differences due to insurance coverage. Int J Health Plann Manage 1999; 14:41-56.
[21] Tu F, Tokunaga S, Deng Z, et al. Analysis of hospital charges for cerebral infarction stroke inpatients in Beijing, People's Republic of China. Health Policy 2002;59:243-56.
[22] Thorpe KE, Howard D. Health insurance and spending among cancer patients. Health Aff (Millwood) 2003;Suppl Web Exclusives:W3-189-98.
[23] Sabatino SA, Coates RJ, Uhler RJ, et al. Health insurance coverage and cost barriers to needed medical care among U.S. adult cancer survivors age<65 years. Cancer 2006;106:2466-75.
[24] Liu X, Mills A. Financing reforms of public health services in China: lessons for other nations. Soc Sci Med 2002;54:1691-8.
[25] Yip W, Eggleston K. Addressing government and market failures with payment incentives: Hospital reimbursement reform in Hainan, China. Soc Sci Med 2004;58:267-77.
[26] Meng Q, Rehnberg C, Zhuang N, et al. The impact of urban health insurance reform on hospital charges: a case study from two cities in China. Health Policy 2004;68:197-209.
[27] Liu X, Hsiao WC. The cost escalation of social health insurance plans in China: its implication for public policy. Soc Sci Med 1995;41:1095-101.
[28] Fine MJ, Pratt HM, Obrosky DS, et al. Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia. Am J Med 2000; 109:378-85.
[29] Reed T Jr, Veith FJ, Gargiulo NJ 3rd, et al. System to decrease length of stay for vascular surgery. J Vasc Surg 2004;39:395-9.
[1]Greenlee RT,Murray T,Bolden S,et aI.Cancer Statistics,2000.CA Cancer J Clin 2000;50:7-33.
[2]Fathalla MF.Incessant ovulation--a factor in ovarian neoplasia? Lancet 1971;2:163.
[3]Cramer DW,Welch WR.Determinants of ovarian cancer risk.Ⅱ.Inferences regarding pathogenesis.J Natl Cancer Inst 1983;71:717-21.
[4]Whiteman DC,Siskind V,Purdie DM,et al.Timing of pregnancy and the risk of epithelial ovarian cancer.Cancer Epidemiol Biomarkers Prev 2003;12:42-6.
[5]Bosetti C,Negri E,Trichopoulos D,et al.Long-term effects of oral contraceptives on ovarian cancer risk.Int J Cancer 2002;102:262-5.
[6]Siskind V,Green A,Bain C,et al.Breastfeeding,menopause,and epithelial ovarian cancer.Epidemiology 1997;8:188-91.
[7]Blumberg J.Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health:Role of Flavonoids in the Diet.J Nutr 2003;133:3244-6.
[8]Ravindranath MH,Saravanan TS,Monteclaro CC,et al.Epicatechins Purified from Green Tea(Camellia sinensis)Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines.Evid Based Complement Alternat Med.2006;3:237-47.
[9]Zhang M,Lee AH,Binns CW,et al.Green tea consumption enhances survival of epithelial ovarian cancer. Int J Cancer 2004;112:465-9.
[10] Binns CW, Zhang M, Lee AH, et al. Green tea consumption enhances survival of epithelial ovarian cancer patients. Asia Pac J Clin Nutr 2004; 13 (Suppl):S116.
[11] Byers T, Marshall J, Graham S, et al. A case-control study of dietary and nondietary factors in ovarian cancer. J Natl Cancer Inst 1983;71:681-6.
[12] Zheng W, Doyle TJ, Kushi LH, et al. Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. Am J Epidemiol 1996; 144:175-82.
[13] Larsson SC, Wolk A. Tea consumption and ovarian cancer risk in a population-based cohort. Arch Intern Med 2005; 165:2683-6.
[14] Miller DR, Rosenberg L, Kaufman DW, et al. Epithelial ovarian cancer and coffee drinking. Int J Epidemiol 1987; 16:13-7.
[15] La Vecchia C, Negri E, Franceschi S, et al. Tea consumption and cancer risk. Nutr Cancer 1992; 17:27-31.
[16] Kuper H, Titus-Ernstoff L, Harlow BL, et al. Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. Int J Cancer 2000; 88:313-8.
[17] Tavani A, Gallus S, Dal Maso L, et al. Coffee and alcohol intake and risk of ovarian cancer: an Italian case-control study. Nutr Cancer 2001;39:29-34.
[18] Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
[19] Goodman MT, Tung KH, McDuffie K, et al. Association of caffeine intake and CYP1A2 genotype with ovarian cancer. Nutr Cancer 2003;46:23-9.
[20] Jordan SJ, Purdie DM, Green AC, et al. Coffee, tea and caffeine and risk of epithelial ovarian cancer. Cancer Causes Control 2004; 15:359-65.
[21] Huh SW, Bae SM, Kim YW, et al. Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines. Gynecol Oncol 2004;94:760-8.
[22] Jung YD, Kim MS, Shin BA, et al. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer 2001;84:844-50.
[23] Zhang G, Miura Y, Yagasaki K. Suppression of adhesion and invasion of hepatoma cells in culture by tea compounds through antioxidative activity. Cancer Lett 2000; 159:169-73.
[24] Saha P, Banerjee S, Ganguly C, et al. Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ. J Environ Pathol Toxicol Oncol 2005 ;24:211-24.
[1]Teede HJ.Hormone replacement therapy and the prevention of cardiovascular disease.Hum Reprod Update 2002;8:201-15.
[2] Wells G, Tugwell P, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 2002;23:529-39.
[3] Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 2003;290:1739-48.
[4] Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047-59.
[5] Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005;365:1543-51.
[6] Whittemore AS, Hsrris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992;136:1212-20.
[7] Garg PP, Kerlikowske K, Subak L, et al. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol 1998;92:472-9.
[8] Coughlin SS, Giustozzi A, Smith SJ, et al. A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol 2000;53:367-75.
[9] Rodriguez C, Patel AV, Calle EE, et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001;285:1460-5.
[10] Lacey JV Jr, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002;288:334-41.
[11] Folsom AR, Anderson JP, Ross JA. Estrogen replacement therapy and ovarian cancer. Epidemiology 2004; 15:100-4.
[12] Bakken K, Alsaker E, Eggen AE, et al. Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer 2004;112:130-4.
[13] Kumle M, Weiderpass E, Braaten T, et al. Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Br J Cancer 2004;90:1386-91.
[14] Lacey JV Jr, Brinton LA, Leitzmann MF, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 2006;98:1397-405.
[15] Danforth KN, Tworoger SS, Hecht JL, et al. A prospective study of postmenopausal hormone use and ovarian cancer risk. Br J Cancer 2007;96:151-6.
[16] Rodriguez C, Calle EE, Coates RJ, et al. Estrogen replacement therapy and fatal ovarian cancer. Am J Epidemiol 1995; 141:828-35.
[17] Hankinson SE, Colditz GA, Hunter DJ, et al. A prospective study of reproductive factors and risk of epithelial ovarian cancer. Cancer 1995;76:284-90.
[18] Mink PJ, Folsom AR, Sellers TA, et al. Physical activity, waist-to-hip ratio, and other risk factors for ovarian cancer: a follow-up study of older women. Epidemiology 1996;7:38-45.
[19] Hoover R, Gray LA Sr, Fraumeni JF Jr. Stilboestrol (diethylstilbestrol) and the risk of ovarian cancer. Lancet 1977;2:533-4.
[20] Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and mortality: long-term follow-up of women in the Walnut Creek Study. Obstet Gynecol 1987;70:289-93.
[21] Adami HO, Persson I, Hoover R, et al. Risk of cancer in women receiving hormone replacement therapy. Int J Cancer 1989;44:833-9.
[22] Hunt K, Vessey M, McPherson K. Mortality in a cohort of long-term users of hormone replacement therapy: an updated analysis. Br J Obstet Gynaecol 1990;971080-6.
[23] Persson I, Yuen J, Bergkvist L, et al. Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy—long-term follow-up of a Swedish cohort. Int J Cancer 1996;67:327-32.
[24] Weiss NS, Lyon JL, Krishnamurthy S, et al. Noncontraceptive estrogen use and the occurrence of ovarian cancer. J Natl Cancer Inst 1982;68:95-8.
[25] Cramer DW, Hutchison GB, Welch WR, et al. Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 1983;71:711-6.
[26] Tzonou A, Day NE, Trichopoulos D, et al. The epidemiology of ovarian cancer in Greece: a case-control study. Eur J Cancer Clin Oncol 1984;20:1045-52.
[27] Hartge P, Hoover R, McGowan L, et al. Menopause and ovarian cancer. Am J Epidemiol 1988;127:990-8.
[28] Kaufman DW, Kelly JP, Welch WR, et al. Noncontraceptive estrogen use and epithelial ovarian cancer. Am J Epidemiol 1989; 130:1142-51.
[29] Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study. Br J Cancer 1989;60:592-8.
[30] Polychronopoulou A, Tzonou A, Hsieh CC, et al. Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. Int J Cancer 1993;55:402-7.
[31]Parazzini F, La Vecchia C, Negri E, et al. Estrogen replacement therapy and ovarian cancer risk. Int J Cancer 1994;57:135-6.
[32]Risch HA. Estrogen replacement therapy and risk of epithelial ovarian cancer. Gynecol Oncol 1996;63:254-7.
[33]Hempling RE, Wong C, Piver MS, et al. Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study. Obstet Gynecol 1997;89:1012-6.
[34] Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, et al. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res 1999;59:3658-62.
[35]Purdie DM, Bain CJ, Siskind V, et al. Hormone replacement therapy and risk of epithelial ovarian cancer. Br J Cancer 1999;81:559-63.
[36]Tavani A, Ricci E, La Vecchia C, et al. Influence of menstrual and reproductive factors on ovarian cancer risk in women with and without family history of breast or ovarian cancer. Int J Epidemiol 2000;29:799-802.
[37]Chiaffarino F, Pelucchi C, Parazzini F, et al. Reproductive and hormonal factors and ovarian cancer. Ann Oncol 2001;12:337-41.
[38] Sit AS, Modugno F, Weissfeld JL, et al. Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma. Gynecol Oncol 2002;86:118-23.
[39]Riman T, Dickman PW, Nilsson S, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst 2002; 94:497-504.
[40] Pike MC, Pearce CL, Peters R, et al. Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 2004;82:186-95.
[41] Mills PK, Riordan DG, Cress RD, et al. Hormone replacement therapy and invasive and borderline epithelial ovarian cancer risk. Cancer Detect Prev 2005 ;29:124-32.
[42] Moorman PG, Schildkraut JM, Calingaert B, et al. Menopausal hormones and risk of ovarian cancer. Am J Obstet Gynecol 2005; 193:76-82.
[43] La Vecchia C, Liberati A, Franceschi S. Noncontraceptive estrogen use and the occurrence of ovarian cancer. J Natl Cancer Inst 1982;69:1207.
[44]Purdie D, Green A, Bain C, et al. Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Int J Cancer 1995;62:678-84,
[45]Risch HA, Marrett LD, Jain M, et al. Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case-control study. Am J Epidemiol 1996;144:363-72.
[46] Wynder EL, Dodo H, Barber HR. Epidemiology of cancer of the ovary. Cancer 1969;23:352-70.
[47]Casagrande JT, Louie EW, Pike MC, et al. "Incessant ovulation" and ovarian cancer. Lancet 1979;2:170-3.
[48]McGowan L, Parent L, Lednar W, et al. The woman at risk for developing ovarian cancer. Gynecol Oncol 1979;7:325-44.
[49]Annegers JF, Strom H, Decker DG, et al. Ovarian cancer: incidence and case-control study. Cancer 1979;43:723-9.
[50]Hildreth NG, Kelsey JL, LiVolsi VA, et al. An epidemiologic study of epithelial carcinoma of the ovary. Am J Epidemiol 1981; 114:398-405.
[51] Rosenberg L, Shapiro S, Slone D, et al. Epithelial ovarian cancer and combination oral contraceptives. JAMA 1982;247:3210-2.
[52]Byers T, Marshall J, Graham S, et al. A case-control study of dietary and nondietary factors in ovarian cancer. J Natl Cancer Inst 1983;71:681-6.
[53] Smith EM, Sowers MF, Burns TL. Effects of smoking on the development of female reproductive cancers. J Natl Cancer Inst 1984;73:371-6.
[54]Nasca PC, Greenwald P, Chorost S, et al. An epidemiologic case-control study of ovarian cancer and reproductive factors. Am J Epidemiol 1984;119:705-13.
[55] Whittemore AS, Wu ML, Paffenbarger RS Jr, et al. Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee. Am J Epidemiol 1988; 128:1228-40.
[56] Beard CM, Hartmann LC, Atkinson EJ, et al. The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935-1991. Ann Epidemiol 2000;10:14-23.
[57]McCann SE, Freudenheim JL, Marshall JR, et al. Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr 2003;133:1937-42.
[58] Tung KH, Goodman MT, Wu AH, et al. Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case-control study. Am J Epidemiol 2003:;158:629-38.
[59]Glud E, Kjaer SK, Thomsen BL, et al. Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer. Arch Intern Med 2004; 164:2253-9.
[60] Kotsopoulos J, Lubinski J, Neuhausen SL, et al. Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol 2006; 100:83-8.
[61] Beral V; Million Women Study Collaborators, Bull D, et al. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007;369:1703-10.
[62] Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-12.
[63]Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 1998;90:1774-86.
[64] Cramer DW, Welch WR. Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst 1983;71:717-21.
[65] O'Donnell AJ, Macleod KG, Burns DJ, et al. Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer 2005;12:851-66.
[1] Parkin DM, Bray F, Ferlay J, et al. Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74-108.
[2] Akhmedkhanov A, Zeleniuch-Jacquotte A, Toniolo P. Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives. Ann NY Acad Sci 2001;943:296-315.
[3] Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005;365:1543-51.
[4] Chang SC, Lacey JV Jr, Brinton LA, et al. Lifetime weight history and endometrial cancer risk by type of menopausal hormone use in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Prev 2007; 16:723-30.
[5] Michnovicz JJ, Hershcopf RJ, Naganuma H, et al. Increased 2- hydroxylation of estradiol as a possible mechanism for the antiestrogenic effect of cigarette smoking. N Engl J Med. 1986;315:1305-9.
[6] Williams RR, Horm JW. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977;58:525-47.
[7] Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose-response data. Stata J 2006;6:40-57.
[8] Williams RR. Horm JW. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977;58:525-47.
[9] Kelsey JL, LiVolsi VA, Holford TR, et al. A case-control study of cancer of the endometrium. Am J Epidemiol 1982; 116:333-42.
[10] Lawrence C, Tessaro I, Durgerian S, et al. Smoking, body weight, and early-stage endometrial cancer. Cancer 1987;59:1665-9.
[11] Levi F, La Vecchia C, Decarli A. Cigarette smoking and the risk of endometrial cancer. Eur J Cancer Clin Oncol 1987;23:1025-9.
[12] Lawrence C, Tessaro I, Durgerian S, et al. Advanced-stage endometrial cancer: contributions of estrogen use, smoking, and other risk factors. Gynecol Oncol 1989;32:41-5.
[13] Swanson CA, Wilbanks GD, Twiggs LB, et al. Moderate alcohol consumption and the risk of endometrial cancer. Epidemiology 1993;4:530-6.
[14] Mills PK, Beeson WL, Phillips RL, et al. Cancer incidence among California Seventh-Day Adventists, 1976-1982. Am J Clin Nutr 1994;59(5 Suppl):1136S-42S.
[15] Kalandidi A, Tzonou A, Lipworth L, et al. A case-control study of endometrial cancer in relation to reproductive, somatometric, and life-style variables. Oncology 1996;53:354-9.
[16] Jain MG, Howe GR, Rohan TE. Nutritional factors and endometrial cancer in Ontario, Canada. Cancer Control 2000;7:288-96.
[17] Parslov M, Lidegaard O, Klintorp S, et al. Risk factors among young women with endometrial cancer: a Danish case-control study. Am J Obstet Gynecol 2000; 182:23-9.
[18] Petridou E, Kedikoglou S, Koukoulomatis P, et al. Diet in relation to endometrial cancer risk: a case-control study in Greece. Nutr Cancer 2002;44:16-22.
[19] Abel EL, Hendrix SL, McNeeley GS, et al. Use of electric blankets and association with prevalence of endometrial cancer. Eur J Cancer Prev. 2007; 16:243-250.
[20] Matthews CE, Xu WH, Zheng W, et al. Physical activity and risk of endometrial cancer: a report from the Shanghai endometrial cancer study. Cancer Epidemiol Biomarkers Prev 2005;14:779-85.
[21] Niwa Y, Ito H, Matsuo K, et al. Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects. Gynecol Oncol 2007; 104:586-90.
[22] Engeland A, Andersen A, Haldorsen T, et al. Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of 26,000 Norwegian men and women. Cancer Causes Control 1996;7:497-506.
[23] Nordlund LA, Carstensen JM, Pershagen G. Cancer incidence in female smokers: a 26-year follow-up. Int J Cancer 1997;73:625-8.
[24] Tulinius H, Sigfusson N, Sigvaldason H, et al. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev 1997;6:863-73.
[25] Terry P, Baron JA, Weiderpass E, et al. Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 1999;82:38-42.
[26] Terry PD, Miller AB, Rohan TE. A prospective cohort study of cigarette smoking and the risk of endometrial cancer. Br J Cancer 2002;86:1430-5.
[27] Folsom AR, Demissie Z, Harnack L; Iowa Women's Health Study. Glycemic index, glycemic load, and incidence of endometrial cancer: the Iowa women's health study. Nutr Cancer 2003;46:119-24.
[28] Viswanathan AN, Feskanich D, De Vivo I, et al. Smoking and the risk of endometrial cancer: results from the Nurses' Health Study. Int J Cancer 2005;114:996-1001.
[29] Loerbroks A, Schouten LJ, Goldbohm RA, et al. Alcohol consumption, cigarette smoking, and endometrial cancer risk: results from the Netherlands Cohort Study. Cancer Causes Control 2007; 18:551-60.
[30] Lacey JV Jr, Leitzmann MF, Chang SC, et al. Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort. Cancer 2007;109:1303-ll.
[31] Setiawan VW, Pike MC, Kolonel LN, et al. Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study. Am J Epidemiol 2007; 165:262-70.
[32] Weiss NS, Farewall VT, Szekely DR, et al. Oestrogens and endometrial cancer: effect of other risk factors on the association. Maturitas 1980;2:185-90.
[33] Smith EM, Sowers MF, Burns TL. Effects of smoking on the development of female reproductive cancers. J Natl Cancer Inst 1984;73:371-6.
[34] Tyler CW, Webster LA, Ory HW, et al. Endometrial cancer: how does cigarette smoking influence the risk of women under age 55 years having this tumor? Am J Obstet Gynecoll985;151:899-905.
[35] Lesko SM, Rosenberg L, Kaufman DW, et al. Cigarette smoking and the risk of endometrial cancer. N Engl J Med 1985;313:593-6.
[36] Baron JA, Byers T, Greenberg ER, et al. Cigarette smoking in women with cancers of the breast and reproductive organs. J Natl Cancer Inst 1986;77:677-80.
[37] Stockwell HG, Lyman GH. Cigarette smoking and the risk of female reproductive cancer. Am J Obstet Gynecol 1987; 157:35-40.
[38] Franks AL, Kendrick JS, Tyler CW. Postmenopausal smoking, estrogen replacement therapy, and the risk of endometrial cancer. Am J Obstet Gynecol 1987; 156:20-3.
[39] Koumantaki Y, Tzonou A, Koumantakis E, et al. A case-control study of cancer of endometrium in Athens. Int J Cancer 1989;43:795-9.
[40] Rubin GL, Peterson HB, Lee NC, et al. Estrogen replacement therapy and the risk of endometrial cancer: remaining controversies. Am J Obstet Gynecol 1990;162:148-54.
[41] Elliott EA, Matanoski GM, Rosenshein NB, et al. Body fat patterning in women with endometrial cancer. Gynecol Oncol 1990;39:253-8.
[42] Shu XO, Brinton LA, Zheng W, et al. A population-based case-control study of endometrial cancer in Shanghai, China. Int J Cancer 1991;49:38-43.
[43] Brinton LA, Barrett RJ, Berman ML, et al. Cigarette smoking and the risk of endometrial cancer. Am J Epidemiol 1993; 137:281-91.
[44] Austin H, Drews C, Partridge EE. A case-control study of endometrial cancer in relation to cigarette smoking, serum estrogen levels, and alcohol use. Am J Obstet Gynecol 1993;169:1086-91.
[45] Weir HK, Sloan M, Kreiger N. The relationship between cigarette smoking and the risk of endometrial neoplasms. Int J Epidemiol 1994;23:261-6.
[46] Parazzini F, La Vecchia C, Negri E, et al. Smoking and risk of endometrial cancer: results from an Italian case-control study. Gynecol Oncol 1995;56:195-9.
[47] Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 1997;146:294-306.
[48] Shields TS, Weiss NS, Voigt LF, et al. The additional risk of endometrial cancer associated with unopposed estrogen use in women with other risk factors. Epidemiology 1999; 10:733-8.
[49] McCann SE, Freudenheim JL, Marshall JR, et al. Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control 2000; 11:965-74.
[50] Newcomer LM, Newcomb PA, Trentham-Dietz A, et al. Hormonal risk factors for endometrial cancer:modification by cigarette smoking(United States).Cancer Causes Control 2001;12:829-35.
[51]Weiderpass E,Baron JA.Cigarette smoking,alcohol consumption,and endometrial cancer risk:a population-based study in Sweden.Cancer Causes Control.2001;12:239-247.
[52]Strom BL,Schinnar R,Weber AL,et al.Case-control study of postmenopausal hormone replacement therapy and endometrial cancer.Am J Epidemiol 2006;164:775-86.
[53]Weiss JM,Saltzman BS,Doherty JA,et al.Risk factors for the incidence of endometrial cancer according to the aggressiveness of disease.Am J Epidemiol 2006;164:56-62.
[54]Okamura C,Tsubono Y,Ito K,et al.Lactation and risk of endometrial cancer in Japan:a case-control study.Tohoku J Exp Med 2006;208:109-115.
[55]Trentham-Dietz A,Nichols HB,Hampton JM,et al.Weight change and risk of endometrial cancer.Int J Epidemiol 2006;35:151-8.
[56]Jensen J,Christiansen C,Rerdbro P.Cigarette smoking,serum estrogens,and bone loss during hormone-replacement therapy after menopause.N Engl J Med 1985;313:973-5.
[57]Cassidenti DL,Vijod AG,Vijod MA,et al.Short-term effects of smoking on the pharmacokinetic profiles of micronized estradiol in postmenopausal women.Am J Obstet Gynecol 1990;163:1953-60.
[58]Akhmedkhanov A,Zeleniuch-Jacquotte A,Toniolo P.Role of exogenous and endogenous hormones in endometrial cancer:review of the evidence and research perspectives.Ann N Y Acad Sci 2001;943:296-315.
[59]Khaw KT,Tazuke S,Barrett-Connor E.Cigarette smoking and levels of adrenal androgens in postmenopausal women.N Engl J Med 1988;318:1705-9.
[60]Matikainen T,Perez GI,Jurisicova A,et al.Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals.Nat Genet 2001;28:355-60.
[61]Mattison DR,Thorgeirsson SS.Smoking and industrial pollution,and their effects on menopause and ovarian cancer.Lancet 1978;1:187-8.
[1]Osborne CK.Tamoxifen in the treatment of breast cancer.N Engl J Med 1998;339:1609-18.
[2]Cuzick J,Powles T,Veronesi U,et al.Overview of the main outcomes in breast-cancer prevention trials.Lancet 2003;361:296-300.
[3]Andersson M,Storm HH,Mouridsen HT.Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer.J Natl Cancer Inst 1991;83:1013-7.
[4]Fisher B,Costantino JP,Redmond CK,et al.Endometrial cancer in tamoxifen-treated breast cancer patients:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP)B-14.J Natl Cancer Inst 1994;86:527-37.
[5]Fisher B,Dignam J,Wolmark N,et al.Tamoxifen in treatment of intraductal breast cancer:National Surgical Adjuvant Breast and Bowel Project B-24randomised controlled trial.Lancet 1999;353:1993-2000.
[6]Andersson M,Kamby C,Jensen MB,et al.Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy.Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial.Eur J Cancer 1999;35:1659-66.
[7]Fisher B,Anderson S,Tan-Chiu E,et al.Tamoxifen and chemotherapy for axillary node-negative,estrogen receptor-negative breast cancer:findings from National Surgical Adjuvant Breast and Bowel Project B-23.J Clin Oncol 2001;19:931-42.
[8]Fisher B,Bryant J,Dignam JJ,et al.Tamoxifen,radiation therapy,or both for prevention of ipsilateral breast rumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.J Clin Oncol 2002;20:4141-9.
[9]Houghton J,George WD,Cuzick J,et al.Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK,Australia,and New Zealand:randomised controlled trial.Lancet 2003;362:95-102.
[10]Baum M,Buzdar A,Cuzick J,et al.Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003;98:1802-10.
[11] Kaufmann M, Graf E, Jonat W, et al. Tamoxifen versus control after adjuvant, risk-adapted chemotherapy in postmenopausal, receptor-negative patients with breast cancer: a randomized trial (GABG-IV D-93)--the German Adjuvant Breast Cancer Group. J Clin Oncol 2005;23:7842-8.
[12] Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-l study. J Natl Cancer Inst 2005;97:1652-62.
[13] Hutchins LF, Green SJ, Ravdin PM, et al. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol 2005;23:8313-21.
[14] Cuzick J, Forbes JF, Sestak I, et al. Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007;99:272-82.
[15] Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007; 99: 283-90.
[16] Rutqvist LE, Johansson H; Stockholm Breast Cancer Study Group. Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol 2007;46:133-45.
[17] Cook LS, Weiss NS, Schwartz SM, et al. Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers. J Natl Cancer Inst 1995;87:1359-64.
[18] Robinson DC, Bloss JD, Schiano MA. A retrospective study of tamoxifen and endometrial cancer in breast cancer patients. Gynecol Oncol 1995; 59: 186-90.
[19] Sasco AJ, Chaplain G, Amoros E, et al. Endometrial cancer following breast cancer: Effect of tamoxifen and castration by radiotherapy. Epidemiology 1996;7:9-13.
[20] Katase K, Sugiyama Y, Hasumi K, et al. The incidence of subsequent endometrial carcinoma with tamoxifen use in patients with primary breast carcinoma. Cancer 1998;82:1698-703.
[21] Mignotte H, Lasset C, Bonadona V, et al. Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC). Int J Cancer 1998;76:325-30.
[22] Newcomb PA, Solomon C, White E. Tamoxifen and risk of large bowel cancer in women with breast cancer. Breast Cancer Res Treat 1999;53:271-7.
[23] Peters-Engl C, Frank W, Danmayr E, et al. Association between endometrial cancer and tamoxifen treatment of breast cancer. Breast Cancer Res Treat 1999;54:255-60.
[24] Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 1999;91:1654-62.
[25] Bergman L, Beelen ML, Gallee MP, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 2000;356:881-7.
[26] Matsuyama Y, Tominaga T, Nomura Y, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann Oncol 2000;11:1537-43.
[27] Ursic Vrscaj M, Kovacic J, Bebar S, et al. Endometrial and other primary cancers after tamoxifen treatment of breast cancer — results of retrospective cohort study. Eur J Obstet Gynecol Reprod Biol 2001 ;95:105-10.
[28] Pukkala E, Kyyronen P, Sankila R, et al. Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study. Int J Cancer 2002; 100:337-41.
[29] Rubino C, de Vathaire F, Shamsaldin A, et al. Radiation dose, chemotherapy, hormonal treatment and risk of second cancer after breast cancer treatment. Br J Cancer 2003 ;89:840-6.
[30] Swerdlow AJ, Jones ME; British Tamoxifen Second Cancer Study Group. Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study. J Natl Cancer Inst 2005;97:375-84.
[31] Sunderland MC, Osborne CK. Tamoxifen in premenopausal patients with metastatic breast cancer: a review. J Clin Oncol 1991;9:1283-97.
[32] Lonning PE, Johannessen DC, Lien EA, et al. Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. J Steroid Biochem Molec Biol 1995;52:491-6.
[33] Gorodeski GI, Barry R, Lunenfeld B, et al. Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. Fertil Steril 1992;57:320-7.
[34] Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 2004;94:256-66.
[35] Dallenbach-Hellweg G, Hahn U. Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antioestrogens (tamoxifen) and gestagens. Int J Gynecol Pathol 1995;14:7-15.
[36] Kedar RP, Bourne TH, Powles TJ, et al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet 1994;343:1318-21.
[37] Ramondetta LM, Palazzo JP, Dunton CJ, et al. A comparative analysis of Ki-67, p53, and p21WAF1CIP1 expression in tamoxifen associated endometrial carcinomas. Anticancer Res 1998;18:4661-5.
[1]Glass GV.Primary,secondary and meta-analysis of research.Education Research.1976;6:3-8.
[2]Fleiss JL,Gross AJ.Meta-analysis in epidemiology.J Clin Epidemiology.1991,44:127-39.
[3]郑利荣.Meta-分析在循证医学应用中应注意的几个问题.现代医院.2004;4:32-3.
[4]Jadad AR,Moore RA,Carroll D,et al.Assessing the quality of reports of randomized clinical trials:is blinding necessary? Control Clin Trials.1996;17:1-12.
[5]Greenland S.Invited commentary.Am J Epidemiol.1994;140:290-6.
[6]Emerson JD,Burdick E,Hoaglin DC,,et al.An empirical study of the possible relation of treatment differences to quality scores in controlled randomized clinical trials.Control Clin Trials.1990;11:339-52.
[7]Stroup DF,Berlin JA,Morton SC,et al.Meta-analysis of observational studies in epidemiology:a proposal for reporting.Meta-analysis Of Observational Studies in Epidemiology(MOOSE)group.JAMA.2000;283:2008-12.
[8]Juni P,Witschi A,Bloch R,et al.The hazards of scoring the quality of clinical trials for meta-analysis.JAMA.1999;282:1054-60.
[9]Gotzsche PC,Hróbjartsson A,Maric K,et al.Data extraction errors in meta-analyses that use standardized mean differences.JAMA.2007;298:430-7.
[10]Hatala R,Keitz S,Wyer P,et al.Tips for learners of evidence-based medicine:4.Assessing heterogeneity of primary studies in systematic reviews and whet her to combine t heir result s.CMAJ,2005,172:661-5.
[11]欧爱华,老膺荣,李晓庆,等.多中心临床随机对照试验的Meta分析.中华流行病学杂志.2005;26:290-3.
[12]Petitti DB.Approaches to heterogeneity in meta-analysis.Stat Med 2001;20:3625-33.
[13]Mantel N,Haenszel W.Statistical aspects of the analysis of data from retrospective studies of disease.J Natl Cancer Inst.1959;22:719-48.
[14]魏丽娟,董惠娟.Meta分析中异质性的识别与处理.第二军医大学学报.2006;27:449-50.
[15]DerSimonian R,Laird N.Meta-analysis in clinical trials.Control Clin Trials 1986;7:177-88.
[16]Dickerson K.The existence of publication bias and risk factors for its occurrence.JAMA.1990;263:1385- 9.
[17]康德英,洪旗,刘关键,等.Meta分析中发表性偏倚的识别与处理.中国循证医学杂志.2003;3:45-9.
[18]Egger M,Smith GD,Schneider M,et al.Bias in meta-analysis detected by a simple,graphical test.BMJ.315:629-34.
[19]Sterne JA,Egger M.Funnel plots for detecting bias in meta-analysis:guidelines on choice of axis.J Clin Epidemiol.2001;54:1046-55.
[20]Phillips CV.Publication bias in situ.BMC Med Res Methodol.2004;4:20.
[21]李河,麦劲壮,方积乾,等.Meta分析中漏斗图的绘制循证医学.2007;7:101-6.
[22]Riley RD,Sutton AJ,Abrams KR,et al.Sensitivity analyses allowed more appropriate and reliable meta-analysis conclusions for multiple outcomes when missing data was present.J Clin Epidemiol.2004;57:911-24.
[23]Copas J,Shi JQ.Meta-analysis,funnel plots and sensitivity analysis.Biostatistics.2000;1:247-62.
[24]Moher D,Cook DJ,Eastwood S,et al.Improving the quality of reports of meta-analyses of randomised controlled trials:the QUOROM statement.Quality of Reporting of Meta-analyses.Lancet.1999;354:1896-900.
[2] Chang S, Long SR, Kutikova L, et al. Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000. J Clin Oncol 2004;22:3524-30.
[3] Zhu H, Yang L, Zhou B, et al. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis 2006;27:2491-6.
[4] Wang B. Major causes of death in China. N Engl J Med 2006;354:874-5.
[5] Wang B, Zhu H, Sun H, et al. Plasma 8-isoprostane concentrations in patients with age-related cataracts. Clin Chem 2005;51:1541-4.
[6] Wang B, Pan J, Wang L, et al. Associations of plasma 8-isoprostane levels with the presence and extent of coronary stenosis in patients with coronary artery disease. Atherosclerosis 2006;184:425-30.
[7] Ho LS. Market reforms and China's health care system. Soc Sci Med 1995;41:1065-72.
[8] Hsiao WC. The Chinese health care system: lessons for other nations. Soc Sci Med 1995;41:1047-55.
[9] Liu Y. Reforming China's urban health insurance system. Health Policy 2002;60:133-50.
[10] Liu Y, Hsiao WC, Eggleston K. Equity in health and health care: the Chinese experience. Soc Sci Med 1999;49:1349-56.
[11] Meng Q, Cheng G, Silver L, et al. The impact of China's retail drug price control policy on hospital expenditures: a case study in two Shandong hospitals. Health Policy Plan 2005;20:185-96.
[12] Gao J, Tang S, Tolhurst R, et al. Changing access to health services in urban China: implications for equity. Health Policy Plan 2001;16:302-12.
[13] Wu M, Xin Y, Wang H, et al. Private and public cross-subsidization: financing Beijing's health-insurance reform. Health Policy 2005;72:41-52
[14] Eggleston K, Yip W. Hospital competition under regulated prices: application to urban health sector reforms in China. Int J Health Care Finance Econ 2004;4:343-68.
[15] Doherty J, Kamae I, Lee KK, et al. What is next for pharmacoeconomics and outcomes research in Asia? Value Health 2004;7:118-32.
[16] Danis M, Linde-Zwirble WT, Astor A, et al. How does lack of insurance affect use of intensive care? A population-based study. Crit Care Med 2006;34:2043-8.
[17] Xu X, Patel DA, Vahratian A, et al. Insurance coverage and health care use among near-elderly women. Womens Health Issues 2006;16:139-48.
[18] Markovitz BP, Andresen EM. Lack of insurance coverage and urgent care use for asthma: a retrospective cohort study. BMC Public Health 2006;6:14.
[19] Boddiger D. Lack of insurance hinders Americans' diabetes care. Lancet 2006;368:15-6.
[20] Dong H, Bogg L, Wang K, et al. A description of outpatient drug use in rural China: evidence of differences due to insurance coverage. Int J Health Plann Manage 1999; 14:41-56.
[21] Tu F, Tokunaga S, Deng Z, et al. Analysis of hospital charges for cerebral infarction stroke inpatients in Beijing, People's Republic of China. Health Policy 2002;59:243-56.
[22] Thorpe KE, Howard D. Health insurance and spending among cancer patients. Health Aff (Millwood) 2003;Suppl Web Exclusives:W3-189-98.
[23] Sabatino SA, Coates RJ, Uhler RJ, et al. Health insurance coverage and cost barriers to needed medical care among U.S. adult cancer survivors age<65 years. Cancer 2006;106:2466-75.
[24] Liu X, Mills A. Financing reforms of public health services in China: lessons for other nations. Soc Sci Med 2002;54:1691-8.
[25] Yip W, Eggleston K. Addressing government and market failures with payment incentives: Hospital reimbursement reform in Hainan, China. Soc Sci Med 2004;58:267-77.
[26] Meng Q, Rehnberg C, Zhuang N, et al. The impact of urban health insurance reform on hospital charges: a case study from two cities in China. Health Policy 2004;68:197-209.
[27] Liu X, Hsiao WC. The cost escalation of social health insurance plans in China: its implication for public policy. Soc Sci Med 1995;41:1095-101.
[28] Fine MJ, Pratt HM, Obrosky DS, et al. Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia. Am J Med 2000; 109:378-85.
[29] Reed T Jr, Veith FJ, Gargiulo NJ 3rd, et al. System to decrease length of stay for vascular surgery. J Vasc Surg 2004;39:395-9.
[1]Greenlee RT,Murray T,Bolden S,et aI.Cancer Statistics,2000.CA Cancer J Clin 2000;50:7-33.
[2]Fathalla MF.Incessant ovulation--a factor in ovarian neoplasia? Lancet 1971;2:163.
[3]Cramer DW,Welch WR.Determinants of ovarian cancer risk.Ⅱ.Inferences regarding pathogenesis.J Natl Cancer Inst 1983;71:717-21.
[4]Whiteman DC,Siskind V,Purdie DM,et al.Timing of pregnancy and the risk of epithelial ovarian cancer.Cancer Epidemiol Biomarkers Prev 2003;12:42-6.
[5]Bosetti C,Negri E,Trichopoulos D,et al.Long-term effects of oral contraceptives on ovarian cancer risk.Int J Cancer 2002;102:262-5.
[6]Siskind V,Green A,Bain C,et al.Breastfeeding,menopause,and epithelial ovarian cancer.Epidemiology 1997;8:188-91.
[7]Blumberg J.Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health:Role of Flavonoids in the Diet.J Nutr 2003;133:3244-6.
[8]Ravindranath MH,Saravanan TS,Monteclaro CC,et al.Epicatechins Purified from Green Tea(Camellia sinensis)Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines.Evid Based Complement Alternat Med.2006;3:237-47.
[9]Zhang M,Lee AH,Binns CW,et al.Green tea consumption enhances survival of epithelial ovarian cancer. Int J Cancer 2004;112:465-9.
[10] Binns CW, Zhang M, Lee AH, et al. Green tea consumption enhances survival of epithelial ovarian cancer patients. Asia Pac J Clin Nutr 2004; 13 (Suppl):S116.
[11] Byers T, Marshall J, Graham S, et al. A case-control study of dietary and nondietary factors in ovarian cancer. J Natl Cancer Inst 1983;71:681-6.
[12] Zheng W, Doyle TJ, Kushi LH, et al. Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. Am J Epidemiol 1996; 144:175-82.
[13] Larsson SC, Wolk A. Tea consumption and ovarian cancer risk in a population-based cohort. Arch Intern Med 2005; 165:2683-6.
[14] Miller DR, Rosenberg L, Kaufman DW, et al. Epithelial ovarian cancer and coffee drinking. Int J Epidemiol 1987; 16:13-7.
[15] La Vecchia C, Negri E, Franceschi S, et al. Tea consumption and cancer risk. Nutr Cancer 1992; 17:27-31.
[16] Kuper H, Titus-Ernstoff L, Harlow BL, et al. Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. Int J Cancer 2000; 88:313-8.
[17] Tavani A, Gallus S, Dal Maso L, et al. Coffee and alcohol intake and risk of ovarian cancer: an Italian case-control study. Nutr Cancer 2001;39:29-34.
[18] Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
[19] Goodman MT, Tung KH, McDuffie K, et al. Association of caffeine intake and CYP1A2 genotype with ovarian cancer. Nutr Cancer 2003;46:23-9.
[20] Jordan SJ, Purdie DM, Green AC, et al. Coffee, tea and caffeine and risk of epithelial ovarian cancer. Cancer Causes Control 2004; 15:359-65.
[21] Huh SW, Bae SM, Kim YW, et al. Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines. Gynecol Oncol 2004;94:760-8.
[22] Jung YD, Kim MS, Shin BA, et al. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer 2001;84:844-50.
[23] Zhang G, Miura Y, Yagasaki K. Suppression of adhesion and invasion of hepatoma cells in culture by tea compounds through antioxidative activity. Cancer Lett 2000; 159:169-73.
[24] Saha P, Banerjee S, Ganguly C, et al. Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ. J Environ Pathol Toxicol Oncol 2005 ;24:211-24.
[1]Teede HJ.Hormone replacement therapy and the prevention of cardiovascular disease.Hum Reprod Update 2002;8:201-15.
[2] Wells G, Tugwell P, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 2002;23:529-39.
[3] Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 2003;290:1739-48.
[4] Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047-59.
[5] Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005;365:1543-51.
[6] Whittemore AS, Hsrris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992;136:1212-20.
[7] Garg PP, Kerlikowske K, Subak L, et al. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol 1998;92:472-9.
[8] Coughlin SS, Giustozzi A, Smith SJ, et al. A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol 2000;53:367-75.
[9] Rodriguez C, Patel AV, Calle EE, et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001;285:1460-5.
[10] Lacey JV Jr, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002;288:334-41.
[11] Folsom AR, Anderson JP, Ross JA. Estrogen replacement therapy and ovarian cancer. Epidemiology 2004; 15:100-4.
[12] Bakken K, Alsaker E, Eggen AE, et al. Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer 2004;112:130-4.
[13] Kumle M, Weiderpass E, Braaten T, et al. Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Br J Cancer 2004;90:1386-91.
[14] Lacey JV Jr, Brinton LA, Leitzmann MF, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 2006;98:1397-405.
[15] Danforth KN, Tworoger SS, Hecht JL, et al. A prospective study of postmenopausal hormone use and ovarian cancer risk. Br J Cancer 2007;96:151-6.
[16] Rodriguez C, Calle EE, Coates RJ, et al. Estrogen replacement therapy and fatal ovarian cancer. Am J Epidemiol 1995; 141:828-35.
[17] Hankinson SE, Colditz GA, Hunter DJ, et al. A prospective study of reproductive factors and risk of epithelial ovarian cancer. Cancer 1995;76:284-90.
[18] Mink PJ, Folsom AR, Sellers TA, et al. Physical activity, waist-to-hip ratio, and other risk factors for ovarian cancer: a follow-up study of older women. Epidemiology 1996;7:38-45.
[19] Hoover R, Gray LA Sr, Fraumeni JF Jr. Stilboestrol (diethylstilbestrol) and the risk of ovarian cancer. Lancet 1977;2:533-4.
[20] Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and mortality: long-term follow-up of women in the Walnut Creek Study. Obstet Gynecol 1987;70:289-93.
[21] Adami HO, Persson I, Hoover R, et al. Risk of cancer in women receiving hormone replacement therapy. Int J Cancer 1989;44:833-9.
[22] Hunt K, Vessey M, McPherson K. Mortality in a cohort of long-term users of hormone replacement therapy: an updated analysis. Br J Obstet Gynaecol 1990;971080-6.
[23] Persson I, Yuen J, Bergkvist L, et al. Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy—long-term follow-up of a Swedish cohort. Int J Cancer 1996;67:327-32.
[24] Weiss NS, Lyon JL, Krishnamurthy S, et al. Noncontraceptive estrogen use and the occurrence of ovarian cancer. J Natl Cancer Inst 1982;68:95-8.
[25] Cramer DW, Hutchison GB, Welch WR, et al. Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 1983;71:711-6.
[26] Tzonou A, Day NE, Trichopoulos D, et al. The epidemiology of ovarian cancer in Greece: a case-control study. Eur J Cancer Clin Oncol 1984;20:1045-52.
[27] Hartge P, Hoover R, McGowan L, et al. Menopause and ovarian cancer. Am J Epidemiol 1988;127:990-8.
[28] Kaufman DW, Kelly JP, Welch WR, et al. Noncontraceptive estrogen use and epithelial ovarian cancer. Am J Epidemiol 1989; 130:1142-51.
[29] Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study. Br J Cancer 1989;60:592-8.
[30] Polychronopoulou A, Tzonou A, Hsieh CC, et al. Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. Int J Cancer 1993;55:402-7.
[31]Parazzini F, La Vecchia C, Negri E, et al. Estrogen replacement therapy and ovarian cancer risk. Int J Cancer 1994;57:135-6.
[32]Risch HA. Estrogen replacement therapy and risk of epithelial ovarian cancer. Gynecol Oncol 1996;63:254-7.
[33]Hempling RE, Wong C, Piver MS, et al. Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study. Obstet Gynecol 1997;89:1012-6.
[34] Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, et al. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res 1999;59:3658-62.
[35]Purdie DM, Bain CJ, Siskind V, et al. Hormone replacement therapy and risk of epithelial ovarian cancer. Br J Cancer 1999;81:559-63.
[36]Tavani A, Ricci E, La Vecchia C, et al. Influence of menstrual and reproductive factors on ovarian cancer risk in women with and without family history of breast or ovarian cancer. Int J Epidemiol 2000;29:799-802.
[37]Chiaffarino F, Pelucchi C, Parazzini F, et al. Reproductive and hormonal factors and ovarian cancer. Ann Oncol 2001;12:337-41.
[38] Sit AS, Modugno F, Weissfeld JL, et al. Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma. Gynecol Oncol 2002;86:118-23.
[39]Riman T, Dickman PW, Nilsson S, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst 2002; 94:497-504.
[40] Pike MC, Pearce CL, Peters R, et al. Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 2004;82:186-95.
[41] Mills PK, Riordan DG, Cress RD, et al. Hormone replacement therapy and invasive and borderline epithelial ovarian cancer risk. Cancer Detect Prev 2005 ;29:124-32.
[42] Moorman PG, Schildkraut JM, Calingaert B, et al. Menopausal hormones and risk of ovarian cancer. Am J Obstet Gynecol 2005; 193:76-82.
[43] La Vecchia C, Liberati A, Franceschi S. Noncontraceptive estrogen use and the occurrence of ovarian cancer. J Natl Cancer Inst 1982;69:1207.
[44]Purdie D, Green A, Bain C, et al. Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Int J Cancer 1995;62:678-84,
[45]Risch HA, Marrett LD, Jain M, et al. Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case-control study. Am J Epidemiol 1996;144:363-72.
[46] Wynder EL, Dodo H, Barber HR. Epidemiology of cancer of the ovary. Cancer 1969;23:352-70.
[47]Casagrande JT, Louie EW, Pike MC, et al. "Incessant ovulation" and ovarian cancer. Lancet 1979;2:170-3.
[48]McGowan L, Parent L, Lednar W, et al. The woman at risk for developing ovarian cancer. Gynecol Oncol 1979;7:325-44.
[49]Annegers JF, Strom H, Decker DG, et al. Ovarian cancer: incidence and case-control study. Cancer 1979;43:723-9.
[50]Hildreth NG, Kelsey JL, LiVolsi VA, et al. An epidemiologic study of epithelial carcinoma of the ovary. Am J Epidemiol 1981; 114:398-405.
[51] Rosenberg L, Shapiro S, Slone D, et al. Epithelial ovarian cancer and combination oral contraceptives. JAMA 1982;247:3210-2.
[52]Byers T, Marshall J, Graham S, et al. A case-control study of dietary and nondietary factors in ovarian cancer. J Natl Cancer Inst 1983;71:681-6.
[53] Smith EM, Sowers MF, Burns TL. Effects of smoking on the development of female reproductive cancers. J Natl Cancer Inst 1984;73:371-6.
[54]Nasca PC, Greenwald P, Chorost S, et al. An epidemiologic case-control study of ovarian cancer and reproductive factors. Am J Epidemiol 1984;119:705-13.
[55] Whittemore AS, Wu ML, Paffenbarger RS Jr, et al. Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee. Am J Epidemiol 1988; 128:1228-40.
[56] Beard CM, Hartmann LC, Atkinson EJ, et al. The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935-1991. Ann Epidemiol 2000;10:14-23.
[57]McCann SE, Freudenheim JL, Marshall JR, et al. Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr 2003;133:1937-42.
[58] Tung KH, Goodman MT, Wu AH, et al. Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case-control study. Am J Epidemiol 2003:;158:629-38.
[59]Glud E, Kjaer SK, Thomsen BL, et al. Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer. Arch Intern Med 2004; 164:2253-9.
[60] Kotsopoulos J, Lubinski J, Neuhausen SL, et al. Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol 2006; 100:83-8.
[61] Beral V; Million Women Study Collaborators, Bull D, et al. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007;369:1703-10.
[62] Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-12.
[63]Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 1998;90:1774-86.
[64] Cramer DW, Welch WR. Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst 1983;71:717-21.
[65] O'Donnell AJ, Macleod KG, Burns DJ, et al. Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer 2005;12:851-66.
[1] Parkin DM, Bray F, Ferlay J, et al. Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74-108.
[2] Akhmedkhanov A, Zeleniuch-Jacquotte A, Toniolo P. Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives. Ann NY Acad Sci 2001;943:296-315.
[3] Beral V, Bull D, Reeves G; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005;365:1543-51.
[4] Chang SC, Lacey JV Jr, Brinton LA, et al. Lifetime weight history and endometrial cancer risk by type of menopausal hormone use in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Prev 2007; 16:723-30.
[5] Michnovicz JJ, Hershcopf RJ, Naganuma H, et al. Increased 2- hydroxylation of estradiol as a possible mechanism for the antiestrogenic effect of cigarette smoking. N Engl J Med. 1986;315:1305-9.
[6] Williams RR, Horm JW. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977;58:525-47.
[7] Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose-response data. Stata J 2006;6:40-57.
[8] Williams RR. Horm JW. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977;58:525-47.
[9] Kelsey JL, LiVolsi VA, Holford TR, et al. A case-control study of cancer of the endometrium. Am J Epidemiol 1982; 116:333-42.
[10] Lawrence C, Tessaro I, Durgerian S, et al. Smoking, body weight, and early-stage endometrial cancer. Cancer 1987;59:1665-9.
[11] Levi F, La Vecchia C, Decarli A. Cigarette smoking and the risk of endometrial cancer. Eur J Cancer Clin Oncol 1987;23:1025-9.
[12] Lawrence C, Tessaro I, Durgerian S, et al. Advanced-stage endometrial cancer: contributions of estrogen use, smoking, and other risk factors. Gynecol Oncol 1989;32:41-5.
[13] Swanson CA, Wilbanks GD, Twiggs LB, et al. Moderate alcohol consumption and the risk of endometrial cancer. Epidemiology 1993;4:530-6.
[14] Mills PK, Beeson WL, Phillips RL, et al. Cancer incidence among California Seventh-Day Adventists, 1976-1982. Am J Clin Nutr 1994;59(5 Suppl):1136S-42S.
[15] Kalandidi A, Tzonou A, Lipworth L, et al. A case-control study of endometrial cancer in relation to reproductive, somatometric, and life-style variables. Oncology 1996;53:354-9.
[16] Jain MG, Howe GR, Rohan TE. Nutritional factors and endometrial cancer in Ontario, Canada. Cancer Control 2000;7:288-96.
[17] Parslov M, Lidegaard O, Klintorp S, et al. Risk factors among young women with endometrial cancer: a Danish case-control study. Am J Obstet Gynecol 2000; 182:23-9.
[18] Petridou E, Kedikoglou S, Koukoulomatis P, et al. Diet in relation to endometrial cancer risk: a case-control study in Greece. Nutr Cancer 2002;44:16-22.
[19] Abel EL, Hendrix SL, McNeeley GS, et al. Use of electric blankets and association with prevalence of endometrial cancer. Eur J Cancer Prev. 2007; 16:243-250.
[20] Matthews CE, Xu WH, Zheng W, et al. Physical activity and risk of endometrial cancer: a report from the Shanghai endometrial cancer study. Cancer Epidemiol Biomarkers Prev 2005;14:779-85.
[21] Niwa Y, Ito H, Matsuo K, et al. Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects. Gynecol Oncol 2007; 104:586-90.
[22] Engeland A, Andersen A, Haldorsen T, et al. Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of 26,000 Norwegian men and women. Cancer Causes Control 1996;7:497-506.
[23] Nordlund LA, Carstensen JM, Pershagen G. Cancer incidence in female smokers: a 26-year follow-up. Int J Cancer 1997;73:625-8.
[24] Tulinius H, Sigfusson N, Sigvaldason H, et al. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev 1997;6:863-73.
[25] Terry P, Baron JA, Weiderpass E, et al. Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 1999;82:38-42.
[26] Terry PD, Miller AB, Rohan TE. A prospective cohort study of cigarette smoking and the risk of endometrial cancer. Br J Cancer 2002;86:1430-5.
[27] Folsom AR, Demissie Z, Harnack L; Iowa Women's Health Study. Glycemic index, glycemic load, and incidence of endometrial cancer: the Iowa women's health study. Nutr Cancer 2003;46:119-24.
[28] Viswanathan AN, Feskanich D, De Vivo I, et al. Smoking and the risk of endometrial cancer: results from the Nurses' Health Study. Int J Cancer 2005;114:996-1001.
[29] Loerbroks A, Schouten LJ, Goldbohm RA, et al. Alcohol consumption, cigarette smoking, and endometrial cancer risk: results from the Netherlands Cohort Study. Cancer Causes Control 2007; 18:551-60.
[30] Lacey JV Jr, Leitzmann MF, Chang SC, et al. Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort. Cancer 2007;109:1303-ll.
[31] Setiawan VW, Pike MC, Kolonel LN, et al. Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study. Am J Epidemiol 2007; 165:262-70.
[32] Weiss NS, Farewall VT, Szekely DR, et al. Oestrogens and endometrial cancer: effect of other risk factors on the association. Maturitas 1980;2:185-90.
[33] Smith EM, Sowers MF, Burns TL. Effects of smoking on the development of female reproductive cancers. J Natl Cancer Inst 1984;73:371-6.
[34] Tyler CW, Webster LA, Ory HW, et al. Endometrial cancer: how does cigarette smoking influence the risk of women under age 55 years having this tumor? Am J Obstet Gynecoll985;151:899-905.
[35] Lesko SM, Rosenberg L, Kaufman DW, et al. Cigarette smoking and the risk of endometrial cancer. N Engl J Med 1985;313:593-6.
[36] Baron JA, Byers T, Greenberg ER, et al. Cigarette smoking in women with cancers of the breast and reproductive organs. J Natl Cancer Inst 1986;77:677-80.
[37] Stockwell HG, Lyman GH. Cigarette smoking and the risk of female reproductive cancer. Am J Obstet Gynecol 1987; 157:35-40.
[38] Franks AL, Kendrick JS, Tyler CW. Postmenopausal smoking, estrogen replacement therapy, and the risk of endometrial cancer. Am J Obstet Gynecol 1987; 156:20-3.
[39] Koumantaki Y, Tzonou A, Koumantakis E, et al. A case-control study of cancer of endometrium in Athens. Int J Cancer 1989;43:795-9.
[40] Rubin GL, Peterson HB, Lee NC, et al. Estrogen replacement therapy and the risk of endometrial cancer: remaining controversies. Am J Obstet Gynecol 1990;162:148-54.
[41] Elliott EA, Matanoski GM, Rosenshein NB, et al. Body fat patterning in women with endometrial cancer. Gynecol Oncol 1990;39:253-8.
[42] Shu XO, Brinton LA, Zheng W, et al. A population-based case-control study of endometrial cancer in Shanghai, China. Int J Cancer 1991;49:38-43.
[43] Brinton LA, Barrett RJ, Berman ML, et al. Cigarette smoking and the risk of endometrial cancer. Am J Epidemiol 1993; 137:281-91.
[44] Austin H, Drews C, Partridge EE. A case-control study of endometrial cancer in relation to cigarette smoking, serum estrogen levels, and alcohol use. Am J Obstet Gynecol 1993;169:1086-91.
[45] Weir HK, Sloan M, Kreiger N. The relationship between cigarette smoking and the risk of endometrial neoplasms. Int J Epidemiol 1994;23:261-6.
[46] Parazzini F, La Vecchia C, Negri E, et al. Smoking and risk of endometrial cancer: results from an Italian case-control study. Gynecol Oncol 1995;56:195-9.
[47] Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 1997;146:294-306.
[48] Shields TS, Weiss NS, Voigt LF, et al. The additional risk of endometrial cancer associated with unopposed estrogen use in women with other risk factors. Epidemiology 1999; 10:733-8.
[49] McCann SE, Freudenheim JL, Marshall JR, et al. Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control 2000; 11:965-74.
[50] Newcomer LM, Newcomb PA, Trentham-Dietz A, et al. Hormonal risk factors for endometrial cancer:modification by cigarette smoking(United States).Cancer Causes Control 2001;12:829-35.
[51]Weiderpass E,Baron JA.Cigarette smoking,alcohol consumption,and endometrial cancer risk:a population-based study in Sweden.Cancer Causes Control.2001;12:239-247.
[52]Strom BL,Schinnar R,Weber AL,et al.Case-control study of postmenopausal hormone replacement therapy and endometrial cancer.Am J Epidemiol 2006;164:775-86.
[53]Weiss JM,Saltzman BS,Doherty JA,et al.Risk factors for the incidence of endometrial cancer according to the aggressiveness of disease.Am J Epidemiol 2006;164:56-62.
[54]Okamura C,Tsubono Y,Ito K,et al.Lactation and risk of endometrial cancer in Japan:a case-control study.Tohoku J Exp Med 2006;208:109-115.
[55]Trentham-Dietz A,Nichols HB,Hampton JM,et al.Weight change and risk of endometrial cancer.Int J Epidemiol 2006;35:151-8.
[56]Jensen J,Christiansen C,Rerdbro P.Cigarette smoking,serum estrogens,and bone loss during hormone-replacement therapy after menopause.N Engl J Med 1985;313:973-5.
[57]Cassidenti DL,Vijod AG,Vijod MA,et al.Short-term effects of smoking on the pharmacokinetic profiles of micronized estradiol in postmenopausal women.Am J Obstet Gynecol 1990;163:1953-60.
[58]Akhmedkhanov A,Zeleniuch-Jacquotte A,Toniolo P.Role of exogenous and endogenous hormones in endometrial cancer:review of the evidence and research perspectives.Ann N Y Acad Sci 2001;943:296-315.
[59]Khaw KT,Tazuke S,Barrett-Connor E.Cigarette smoking and levels of adrenal androgens in postmenopausal women.N Engl J Med 1988;318:1705-9.
[60]Matikainen T,Perez GI,Jurisicova A,et al.Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals.Nat Genet 2001;28:355-60.
[61]Mattison DR,Thorgeirsson SS.Smoking and industrial pollution,and their effects on menopause and ovarian cancer.Lancet 1978;1:187-8.
[1]Osborne CK.Tamoxifen in the treatment of breast cancer.N Engl J Med 1998;339:1609-18.
[2]Cuzick J,Powles T,Veronesi U,et al.Overview of the main outcomes in breast-cancer prevention trials.Lancet 2003;361:296-300.
[3]Andersson M,Storm HH,Mouridsen HT.Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer.J Natl Cancer Inst 1991;83:1013-7.
[4]Fisher B,Costantino JP,Redmond CK,et al.Endometrial cancer in tamoxifen-treated breast cancer patients:findings from the National Surgical Adjuvant Breast and Bowel Project(NSABP)B-14.J Natl Cancer Inst 1994;86:527-37.
[5]Fisher B,Dignam J,Wolmark N,et al.Tamoxifen in treatment of intraductal breast cancer:National Surgical Adjuvant Breast and Bowel Project B-24randomised controlled trial.Lancet 1999;353:1993-2000.
[6]Andersson M,Kamby C,Jensen MB,et al.Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy.Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial.Eur J Cancer 1999;35:1659-66.
[7]Fisher B,Anderson S,Tan-Chiu E,et al.Tamoxifen and chemotherapy for axillary node-negative,estrogen receptor-negative breast cancer:findings from National Surgical Adjuvant Breast and Bowel Project B-23.J Clin Oncol 2001;19:931-42.
[8]Fisher B,Bryant J,Dignam JJ,et al.Tamoxifen,radiation therapy,or both for prevention of ipsilateral breast rumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.J Clin Oncol 2002;20:4141-9.
[9]Houghton J,George WD,Cuzick J,et al.Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK,Australia,and New Zealand:randomised controlled trial.Lancet 2003;362:95-102.
[10]Baum M,Buzdar A,Cuzick J,et al.Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003;98:1802-10.
[11] Kaufmann M, Graf E, Jonat W, et al. Tamoxifen versus control after adjuvant, risk-adapted chemotherapy in postmenopausal, receptor-negative patients with breast cancer: a randomized trial (GABG-IV D-93)--the German Adjuvant Breast Cancer Group. J Clin Oncol 2005;23:7842-8.
[12] Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-l study. J Natl Cancer Inst 2005;97:1652-62.
[13] Hutchins LF, Green SJ, Ravdin PM, et al. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol 2005;23:8313-21.
[14] Cuzick J, Forbes JF, Sestak I, et al. Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007;99:272-82.
[15] Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007; 99: 283-90.
[16] Rutqvist LE, Johansson H; Stockholm Breast Cancer Study Group. Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol 2007;46:133-45.
[17] Cook LS, Weiss NS, Schwartz SM, et al. Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers. J Natl Cancer Inst 1995;87:1359-64.
[18] Robinson DC, Bloss JD, Schiano MA. A retrospective study of tamoxifen and endometrial cancer in breast cancer patients. Gynecol Oncol 1995; 59: 186-90.
[19] Sasco AJ, Chaplain G, Amoros E, et al. Endometrial cancer following breast cancer: Effect of tamoxifen and castration by radiotherapy. Epidemiology 1996;7:9-13.
[20] Katase K, Sugiyama Y, Hasumi K, et al. The incidence of subsequent endometrial carcinoma with tamoxifen use in patients with primary breast carcinoma. Cancer 1998;82:1698-703.
[21] Mignotte H, Lasset C, Bonadona V, et al. Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC). Int J Cancer 1998;76:325-30.
[22] Newcomb PA, Solomon C, White E. Tamoxifen and risk of large bowel cancer in women with breast cancer. Breast Cancer Res Treat 1999;53:271-7.
[23] Peters-Engl C, Frank W, Danmayr E, et al. Association between endometrial cancer and tamoxifen treatment of breast cancer. Breast Cancer Res Treat 1999;54:255-60.
[24] Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 1999;91:1654-62.
[25] Bergman L, Beelen ML, Gallee MP, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 2000;356:881-7.
[26] Matsuyama Y, Tominaga T, Nomura Y, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann Oncol 2000;11:1537-43.
[27] Ursic Vrscaj M, Kovacic J, Bebar S, et al. Endometrial and other primary cancers after tamoxifen treatment of breast cancer — results of retrospective cohort study. Eur J Obstet Gynecol Reprod Biol 2001 ;95:105-10.
[28] Pukkala E, Kyyronen P, Sankila R, et al. Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study. Int J Cancer 2002; 100:337-41.
[29] Rubino C, de Vathaire F, Shamsaldin A, et al. Radiation dose, chemotherapy, hormonal treatment and risk of second cancer after breast cancer treatment. Br J Cancer 2003 ;89:840-6.
[30] Swerdlow AJ, Jones ME; British Tamoxifen Second Cancer Study Group. Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study. J Natl Cancer Inst 2005;97:375-84.
[31] Sunderland MC, Osborne CK. Tamoxifen in premenopausal patients with metastatic breast cancer: a review. J Clin Oncol 1991;9:1283-97.
[32] Lonning PE, Johannessen DC, Lien EA, et al. Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. J Steroid Biochem Molec Biol 1995;52:491-6.
[33] Gorodeski GI, Barry R, Lunenfeld B, et al. Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. Fertil Steril 1992;57:320-7.
[34] Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 2004;94:256-66.
[35] Dallenbach-Hellweg G, Hahn U. Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antioestrogens (tamoxifen) and gestagens. Int J Gynecol Pathol 1995;14:7-15.
[36] Kedar RP, Bourne TH, Powles TJ, et al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet 1994;343:1318-21.
[37] Ramondetta LM, Palazzo JP, Dunton CJ, et al. A comparative analysis of Ki-67, p53, and p21WAF1CIP1 expression in tamoxifen associated endometrial carcinomas. Anticancer Res 1998;18:4661-5.
[1]Glass GV.Primary,secondary and meta-analysis of research.Education Research.1976;6:3-8.
[2]Fleiss JL,Gross AJ.Meta-analysis in epidemiology.J Clin Epidemiology.1991,44:127-39.
[3]郑利荣.Meta-分析在循证医学应用中应注意的几个问题.现代医院.2004;4:32-3.
[4]Jadad AR,Moore RA,Carroll D,et al.Assessing the quality of reports of randomized clinical trials:is blinding necessary? Control Clin Trials.1996;17:1-12.
[5]Greenland S.Invited commentary.Am J Epidemiol.1994;140:290-6.
[6]Emerson JD,Burdick E,Hoaglin DC,,et al.An empirical study of the possible relation of treatment differences to quality scores in controlled randomized clinical trials.Control Clin Trials.1990;11:339-52.
[7]Stroup DF,Berlin JA,Morton SC,et al.Meta-analysis of observational studies in epidemiology:a proposal for reporting.Meta-analysis Of Observational Studies in Epidemiology(MOOSE)group.JAMA.2000;283:2008-12.
[8]Juni P,Witschi A,Bloch R,et al.The hazards of scoring the quality of clinical trials for meta-analysis.JAMA.1999;282:1054-60.
[9]Gotzsche PC,Hróbjartsson A,Maric K,et al.Data extraction errors in meta-analyses that use standardized mean differences.JAMA.2007;298:430-7.
[10]Hatala R,Keitz S,Wyer P,et al.Tips for learners of evidence-based medicine:4.Assessing heterogeneity of primary studies in systematic reviews and whet her to combine t heir result s.CMAJ,2005,172:661-5.
[11]欧爱华,老膺荣,李晓庆,等.多中心临床随机对照试验的Meta分析.中华流行病学杂志.2005;26:290-3.
[12]Petitti DB.Approaches to heterogeneity in meta-analysis.Stat Med 2001;20:3625-33.
[13]Mantel N,Haenszel W.Statistical aspects of the analysis of data from retrospective studies of disease.J Natl Cancer Inst.1959;22:719-48.
[14]魏丽娟,董惠娟.Meta分析中异质性的识别与处理.第二军医大学学报.2006;27:449-50.
[15]DerSimonian R,Laird N.Meta-analysis in clinical trials.Control Clin Trials 1986;7:177-88.
[16]Dickerson K.The existence of publication bias and risk factors for its occurrence.JAMA.1990;263:1385- 9.
[17]康德英,洪旗,刘关键,等.Meta分析中发表性偏倚的识别与处理.中国循证医学杂志.2003;3:45-9.
[18]Egger M,Smith GD,Schneider M,et al.Bias in meta-analysis detected by a simple,graphical test.BMJ.315:629-34.
[19]Sterne JA,Egger M.Funnel plots for detecting bias in meta-analysis:guidelines on choice of axis.J Clin Epidemiol.2001;54:1046-55.
[20]Phillips CV.Publication bias in situ.BMC Med Res Methodol.2004;4:20.
[21]李河,麦劲壮,方积乾,等.Meta分析中漏斗图的绘制循证医学.2007;7:101-6.
[22]Riley RD,Sutton AJ,Abrams KR,et al.Sensitivity analyses allowed more appropriate and reliable meta-analysis conclusions for multiple outcomes when missing data was present.J Clin Epidemiol.2004;57:911-24.
[23]Copas J,Shi JQ.Meta-analysis,funnel plots and sensitivity analysis.Biostatistics.2000;1:247-62.
[24]Moher D,Cook DJ,Eastwood S,et al.Improving the quality of reports of meta-analyses of randomised controlled trials:the QUOROM statement.Quality of Reporting of Meta-analyses.Lancet.1999;354:1896-900.