河南安阳高发区食管鳞癌发病风险与雌激素的关系
摘要
1.研究背景：
食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)是世界上最常见的六大恶性肿瘤之一,显著的地域性性分布差异和家族聚集现象提示环境和遗传因素在食管癌的发病机制上均起重要作用。80年代以来,尤其近10年,这些地区居民经济、生活环境和水平以及医疗条件等已发生巨大变化,但是关于不同时间ESCC发病性别比情况,尚缺乏大样本量报道。
ESCC男性发病率高于女性,性激素可能是导致ESCC男女发病率不同主要因素之一,其中雌激素可能起保护作用。体内雌激素水平随年龄的增长而不断变化,女性闭经后显著下降。因此,年龄可以作为衡量体内雌激素含量的指标,反映出体内雌激素的水平。
本研究旨在通过分析1975-2007年间河南安阳食管癌高发区患者性别比的情况,了解性别与ESCC发病风险的关系。在此基础上,利用放射免疫测定法检测部分患者血清雌激素水平和免疫组化技术观察组织中雌激素受体表达情况,进一步探讨其在食管癌发生中的作用。
2.材料与方法
2.1研究对象15363例ESCC均来自于1975-2007安阳市肿瘤医院住院资料：1975-1997(男3671例,平均年龄57±10岁；女2615例,平均年龄57±9岁)；1998-2007(男5429例,平均年龄60±10岁；女3648例,平均年龄61±10岁)。血清、食管癌手术切除标本均来自安阳ESCC患者,(男87例,平均年龄54±7岁；女45例,平均年龄55±7岁)。
2.2统计学处理
本研究采用SPSS17.0软件对资料进行统计学分析,统计结果的显著性检验水准a=0.05。
3.结果：
3.1家族史阳／阴性患者均在小于50岁组中男女比例最高,且随年龄增加而降低,差异具有统计学意义χ2=16.8,df=3,P<0.05；χ2=26.1,df=3,P<0.05)。
3.21975-1997年小于50岁患者男女比例最高,且随年龄增加而降低,差异无统计学意义(χ2=6.0,df=3,P>0.05);1998-2007年小于50岁患者男女比例最高,且随年龄增加而降低,差异亦具有统计学意义(χ2=44.9,df=3,P<0.05)。
3.3雌激素广泛存在于食管癌高发区患者血清中,且雌激素受体在高发区食管癌患者正常、癌前病变、癌组织中均有不同程度的表达。
4.结论：
ESCC小于50岁患者男女比例最高,且随年龄增加而降低,提示体内雌激素水平的差异可能是ESCC男女发病率不同的原因,因为闭经后其对女性的保护作用明显下降。血清雌激素检测和免疫组化结果提示,雌激素的变化可能是食管癌变的重要机制之一。
1. Background
Esophageal squamous cell carcinoma (ESCC) is the sixth common cause of cancer-related deaths in the world with remarkable variations in incidence by geographic and ethnic divisions which have shown the importance of environmental and genetic factors in the pathogenesis of ESCC. Since1980s, the socio-economic status, living and medical condition of resident in these areas have been improved greatly especially last10years. However, there was little document on the impact of environment changes on sex ratio of ESCC incidence, particularly lack large sample data from HIA along with time changes.
There is a striking male predominance in esophageal cancer patients. Sex hormones have been proposed as a possible explanation for the male predominance in esophageal cancer, with possible protective effects for estrogen. Estrogen production abruptly decrease with menopause in females. Since endogenous estrogen production varies with age, age can be used as a proxy for estrogen exposure.
Thus, the aim of present study was undertaken in sex ratio of patients with esophageal cancer in HLI of Anyang during the1975-2007to find out the relationship between risk of ESCC and Gender. On this basis, radioimmunoassay (RIA) was used to determine the serum level of estrogen in patients with esophageal cancer from high-incidence area (HIA) and immunohistochemical estrogen receptor expression, to further explore its role in esophageal cancer.
2. Materials and methods
2.1Materials
2.1.115363patients with ESCC in this study were from Anyang Tumor Hospital information during the1975-2007.3671were males and2615were females, with a mean age of57±10years in male and57±9years in female during the1975-1997.5429were males and3648were females, with a mean age of57±10years in male and57±9years in female during the1998-2007. This study included132patients with ESCC, All the patients were from Anyang, Henan, the highest incidence area in northern China, and were confirmed with ESCC by histopathologist. Of the patients with ESCC, there were87males and45females with a mean age of53.7±7.3and54.7±6.6, respectively.
2.2Methods
The appropriate application of social science statistical software package SPSS17.0was used for statistical analysis of data. P value with less than0.05was considered significant.
3. Results
3.1The sex ratios of the familial cases were highest in the age of <50years, declined with age, and was statistical significance (x2=16.8, df=2,P<0.05; x2=26.1, df=3,P<0.05)。
3.2The sex ratios were highest in the age of<50years during the1975-1997, declined with age, and was not statistical significance (x2=6.0, df=3, P>0.05); The sex ratios were highest in the age of<50years during the1997-2007, declined with age, and was not statistical significance (x2=44.9, df=3,P<0.05)
3.3Estrogen exists widely in esophageal cancer patients'serum in high incidence area. And estrogen receptor expression is different levels in the normal, precancerous lesions, cancer of esophageal cancer patients in high incidence.
4. Conclusions
The sex ratios of ESCC were highest in the age of<50years, declined with age, estrogen have been proposed as a possible explanation for the male predominance in esophageal cancer, Estrogen production abruptly decrease with menopause in females. Serum estrogen and immunohistochemical detection results suggest that changes in estrogen may be an important mechanism of esophageal carcinogenesis.
食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)是世界上最常见的六大恶性肿瘤之一,显著的地域性性分布差异和家族聚集现象提示环境和遗传因素在食管癌的发病机制上均起重要作用。80年代以来,尤其近10年,这些地区居民经济、生活环境和水平以及医疗条件等已发生巨大变化,但是关于不同时间ESCC发病性别比情况,尚缺乏大样本量报道。
ESCC男性发病率高于女性,性激素可能是导致ESCC男女发病率不同主要因素之一,其中雌激素可能起保护作用。体内雌激素水平随年龄的增长而不断变化,女性闭经后显著下降。因此,年龄可以作为衡量体内雌激素含量的指标,反映出体内雌激素的水平。
本研究旨在通过分析1975-2007年间河南安阳食管癌高发区患者性别比的情况,了解性别与ESCC发病风险的关系。在此基础上,利用放射免疫测定法检测部分患者血清雌激素水平和免疫组化技术观察组织中雌激素受体表达情况,进一步探讨其在食管癌发生中的作用。
2.材料与方法
2.1研究对象15363例ESCC均来自于1975-2007安阳市肿瘤医院住院资料：1975-1997(男3671例,平均年龄57±10岁；女2615例,平均年龄57±9岁)；1998-2007(男5429例,平均年龄60±10岁；女3648例,平均年龄61±10岁)。血清、食管癌手术切除标本均来自安阳ESCC患者,(男87例,平均年龄54±7岁；女45例,平均年龄55±7岁)。
2.2统计学处理
本研究采用SPSS17.0软件对资料进行统计学分析,统计结果的显著性检验水准a=0.05。
3.结果：
3.1家族史阳／阴性患者均在小于50岁组中男女比例最高,且随年龄增加而降低,差异具有统计学意义χ2=16.8,df=3,P<0.05；χ2=26.1,df=3,P<0.05)。
3.21975-1997年小于50岁患者男女比例最高,且随年龄增加而降低,差异无统计学意义(χ2=6.0,df=3,P>0.05);1998-2007年小于50岁患者男女比例最高,且随年龄增加而降低,差异亦具有统计学意义(χ2=44.9,df=3,P<0.05)。
3.3雌激素广泛存在于食管癌高发区患者血清中,且雌激素受体在高发区食管癌患者正常、癌前病变、癌组织中均有不同程度的表达。
4.结论：
ESCC小于50岁患者男女比例最高,且随年龄增加而降低,提示体内雌激素水平的差异可能是ESCC男女发病率不同的原因,因为闭经后其对女性的保护作用明显下降。血清雌激素检测和免疫组化结果提示,雌激素的变化可能是食管癌变的重要机制之一。
1. Background
Esophageal squamous cell carcinoma (ESCC) is the sixth common cause of cancer-related deaths in the world with remarkable variations in incidence by geographic and ethnic divisions which have shown the importance of environmental and genetic factors in the pathogenesis of ESCC. Since1980s, the socio-economic status, living and medical condition of resident in these areas have been improved greatly especially last10years. However, there was little document on the impact of environment changes on sex ratio of ESCC incidence, particularly lack large sample data from HIA along with time changes.
There is a striking male predominance in esophageal cancer patients. Sex hormones have been proposed as a possible explanation for the male predominance in esophageal cancer, with possible protective effects for estrogen. Estrogen production abruptly decrease with menopause in females. Since endogenous estrogen production varies with age, age can be used as a proxy for estrogen exposure.
Thus, the aim of present study was undertaken in sex ratio of patients with esophageal cancer in HLI of Anyang during the1975-2007to find out the relationship between risk of ESCC and Gender. On this basis, radioimmunoassay (RIA) was used to determine the serum level of estrogen in patients with esophageal cancer from high-incidence area (HIA) and immunohistochemical estrogen receptor expression, to further explore its role in esophageal cancer.
2. Materials and methods
2.1Materials
2.1.115363patients with ESCC in this study were from Anyang Tumor Hospital information during the1975-2007.3671were males and2615were females, with a mean age of57±10years in male and57±9years in female during the1975-1997.5429were males and3648were females, with a mean age of57±10years in male and57±9years in female during the1998-2007. This study included132patients with ESCC, All the patients were from Anyang, Henan, the highest incidence area in northern China, and were confirmed with ESCC by histopathologist. Of the patients with ESCC, there were87males and45females with a mean age of53.7±7.3and54.7±6.6, respectively.
2.2Methods
The appropriate application of social science statistical software package SPSS17.0was used for statistical analysis of data. P value with less than0.05was considered significant.
3. Results
3.1The sex ratios of the familial cases were highest in the age of <50years, declined with age, and was statistical significance (x2=16.8, df=2,P<0.05; x2=26.1, df=3,P<0.05)。
3.2The sex ratios were highest in the age of<50years during the1975-1997, declined with age, and was not statistical significance (x2=6.0, df=3, P>0.05); The sex ratios were highest in the age of<50years during the1997-2007, declined with age, and was not statistical significance (x2=44.9, df=3,P<0.05)
3.3Estrogen exists widely in esophageal cancer patients'serum in high incidence area. And estrogen receptor expression is different levels in the normal, precancerous lesions, cancer of esophageal cancer patients in high incidence.
4. Conclusions
The sex ratios of ESCC were highest in the age of<50years, declined with age, estrogen have been proposed as a possible explanation for the male predominance in esophageal cancer, Estrogen production abruptly decrease with menopause in females. Serum estrogen and immunohistochemical detection results suggest that changes in estrogen may be an important mechanism of esophageal carcinogenesis.
引文
[1]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J Clin.2005.55(2): 74-108.
[2]Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer.2002.102(3):271-4.
[3]王立东.河南食管癌研究的理解和思考.郑州大学学报：医学学版.2006.41(1)：1-5.
[4]Wang LD, Hong JY, Qiu SL, Gao H, Yang CS. Accumulation of p53 protein in human esophageal precancerous lesions:a possible early biomarker for carcinogenesis. Cancer Res.1993.53(8):1783-7.
[5]Wang LD, Zhou Q, Yang CS. Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area. J Cell Biochem Suppl.1997.28-29:159-65.
[6]Correa P. Precursors of gastric and esophageal cancer. Cancer.1982.50(11 Suppl):2554-65.
[7]杜百廉主编.食管癌.1994.30-107.
[8]Zhang W, Press OA, Haiman CA, et al. Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. J Clin Oncol.2007. 25(24):3726-31.
[9]李光恒.食管／贲门癌家族性与保护人群(山西阳城肿瘤防治点调查报告).肿瘤防治研究.1980.2(6)：1-6.
[10]Parkin DM LE, Muir CS. Estimate of the worldwide frequency of sixteen major cancers in 1980. In J Cancer.1988.41(2):184-197.
[11]李卫东,张春林.山西省阳泉市部分人口食管癌遗传流行病学调查.中华医学杂志.1998.78(3)：203-206.
[12]Gao Y, Hu N, Han X, et al. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China. BMC Cancer.2009.9:269.
[13]Liu M, Su M, Tian DP, Zhang GH, Yang HL, Gao YX. Heredity, diet and lifestyle as determining risk factors for the esophageal cancer on Nanao Island in Southern China. Fam Cancer.2010.9(2):229-38.
[14]Wen D, Wang S, Zhang L, Wei L, Zhou W, Peng Q. Early onset, multiple primary malignancies, and poor prognosis are indicative of an inherited predisposition to esophageal squamous cell carcinoma for the familial as opposed to the sporadic cases--an update on over 14-year survival. Eur J Med Genet.2009. 52(6):381-5.
[15]王立东[1],樊慧[1],焦新英[2]等.河南食管癌高发区95对单卵双胞胎疾病谱和2323例食管癌患者家族史调查.中华肿瘤防治杂志.2006.13(20)：1521-1524.
[16]Available at:http://www.who.int/gender/whatisgender/en/. Accessed July 1,2011.
[17]Cancer statistics 2011. CA Cancer J Clin.Available at:http://www.cacancerjournal.com. Accessed July 1, 2011.
[18]Rutegard M, Shore R, Lu Y, Lagergren P, Lindblad M. Sex differences in the incidence of gastrointestinal adenocarcinoma in Sweden 1970-2006. Eur J Cancer.2010.46(6):1093-100.
[19]Derakhshan MH, Liptrot S, Paul J, Brown IL, Morrison D, McColl K.E. Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. Gut.2009.58(1):16-23.
[20]World cancer research fund international:General world cancer statistics. Available at: http://www.wcrf.org/world_cancer_statistics.php. Accessed July 1,2011.
[21]Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries,1973-1995. Int J Cancer.2002.99(6):860-8.
[22]Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer.1999.83(1):18-29.
[23]Wang LD, Shi ST, Zhou Q, et al. Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. Int J Cancer.1994.59(4):514-9.
[24]Holmes RS, Vaughan TL. Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol.2007. 17(1):2-9.
[25]Li JY. Epidemiology of esophageal cancer in China. Natl Cancer Inst Monogr.1982.62:113-20.
[26]Sugimachi K, Matsuoka H, Matsufuji H, Maekawa S, Kai H, Okudaira Y. Survival rates of women with carcinoma of the esophagus exceed those of men. Surg Gynecol Obstet.1987.164(6):541-4.
[27]Micheli A, Mariotto A, Giorgi RA, Gatta G, Muti P. The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group. Eur J Cancer.1998.34(14 Spec No):2271-8.
[28]Rohatgi PR, Correa AM, Swisher SG, et al. Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation:differences in presentation and therapy outcome. Dis Esophagus. 2006.19(3):152-7.
[29]杨科,崔树德,李连方.乳腺癌组织中ER. PR、Ps2、C-erbB-2表达与新辅助化疗疗效的关系.山东医药.2011.51(6)：18-19.
[30]Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science.2001.291(5507): 1304-51.
[31]Brinton RD. Estrogen regulation of glucose metabolism and mitochondrial function:therapeutic implications for prevention of Alzheimer's disease. Adv Drug Deliv Rev.2008.60(13-14):1504-11.
[32]Kumar DM, Simpkins JW, Agarwal N. Estrogens and neuroprotection in retinal diseases. Mol Vis.2008. 14:1480-6.
[33]Hojo Y, Murakami G, Mukai H, et al. Estrogen synthesis in the brain--role in synaptic plasticity and memory. Mol Cell Endocrinol.2008.290(1-2):31-43.
[34]Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events:a meta-analysis. Eur Heart J.2008.29(16):2031-41.
[35]Birge SJ. Hormone therapy and stroke. Clin Obstet Gynecol.2008.51(3):581-91.
[36]Deurveilher S, Cumyn EM, Peers T, Rusak B, Semba K. Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats. Am J Physiol Regul Integr Comp Physiol.2008.295(4):R1328-40.
[37]Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet Gynecol.2009.113(1):74-80.
[38]Suzuki F, Akahira J, Miura I, et al. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma. Cancer Sci.2008.99(12):2365-72.
[39]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[40]Winter DC, Taylor C, C OG, Harvey BJ. Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon. Br J Surg.2000.87(12):1684-9.
[41]Simoncini T, Genazzani AR. Non-genomic actions of sex steroid hormones. Eur J Endocrinol.2003. 148(3):281-92.
[42]Moggs JG, Orphanides G. Estrogen receptors:orchestrators of pleiotropic cellular responses. EMBO Rep. 2001.2(9):775-81.
[43]Alzamora R, Harvey BJ. Direct binding and activation of protein kinase C isoforms by steroid hormones. Steroids.2008.73(9-10):885-8.
[44]Muchekehu RW, Harvey BJ.17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3. Cell Calcium.2008.44(3):276-88.
[45]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[46]Ropero AB, Fuentes E, Rovira JM, Ripoll C, Soria B, Nadal A. Non-genomic actions of 17beta-oestradiol in mouse pancreatic beta-cells are mediated by a cGMP-dependent protein kinase. J Physiol.1999.521 Pt 2:397-407.
[47]Simoncini T, Varone G, Fornari L, et al. Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a.fourth-generation selective estrogen receptor modulator. Endocrinology.2002.143(6):2052-61.
[48]Hennessy BA, Harvey BJ, Healy V.17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Mol Cell Endocrinol.2005.229(1-2):39-47.
[49]Rutegard M, Nordenstedt H, Lu Y, Lagergren J, Lagergren P. Sex-specific exposure prevalence of established risk factors for oesophageal adenocarcinoma. Br J Cancer.2010.103(5):735-40.
[50]Lofdahl HE, Lu Y, Lagergren J. Sex-specific risk factor profile in oesophageal adenocarcinoma. Br J Cancer.2008.99(9):1506-10.
[51]Freedman ND, Derakhshan MH, Abnet CC, Schatzkin A, Hollenbeck AR, McColl KE. Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women. Eur J Cancer.2010.46(13):2473-8.
[52]Cheng KK, Sharp L, McKinney PA, et al. A case-control study of oesophageal adenocarcinoma in women: a preventable disease. Br J Cancer.2000.83(1):127-32.
[53]Scapa E, Broide E, Waron M, Klinowski E, Eshchar J. Esophagogastric mucosal junction (EGMJ):its location as measured by endoscopy. Surg Laparosc Endosc.1997.7(2):159-61.
[54]Li Q, Castell JA, Castell DO. Manometric determination of esophageal length. Am J Gastroenterol.1994. 89(5):722-5.
[55]van HMA, Katz PO, Gideon RM, et al. Are manometric parameters of the upper esophageal sphincter and pharynx affected by age and gender. Dysphagia.2003.18(3):211-7.
[56]McKee GJ, Johnston BT, McBride GB, Primrose WJ. Does age or sex affect pharyngeal swallowing. Clin Otolaryngol Allied Sci.1998.23(2):100-6.
[57]Vega KJ, Palacio C, Langford-Legg T, Watts J, Jamal MM. Gender variation in oesophageal motor function:analysis of 129 healthy individuals. Dig Liver Dis.2010.42(7):482-4.
[58]COX AJ. Stomach size and its relation to chronic peptic ulcer. AMA Arch Pathol.1952.54(5):407-22.
[59]Richter JE, Bradley LA, DeMeester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender. Dig Dis Sci.1992.37(6):849-56.
[60]Fass R, Sampliner RE, Mackel C, McGee D, Rappaport W. Age-and gender-related differences in 24-hour esophageal pH monitoring of normal subjects. Dig Dis Sci.1993.38(10):1926-8.
[61]Ter RB, Johnston BT, Castell DO. Influence of age and gender on gastroesophageal reflux in symptomatic patients. Dis Esophagus.1998.11(2):106-8.
[62]Rocha LP, de Melo E Silva AT, Gomes NC, et al. The influence of gender and of AIDS on the immunity of autopsied patients'esophagus. AIDS Res Hum Retroviruses.2011.27(5):511-8.
[63]Nguyen P, Lee SD, Castell DO. Evidence of gender differences in esophageal pain threshold. Am J Gastroenterol.1995.90(6):901-5.
[64]Rao SS, Mudipalli RS, Mujica VR, Patel RS, Zimmerman B. Effects of gender and age on esophageal biomechanical properties and sensation. Am J Gastroenterol.2003.98(8):1688-95.
[65]Reddy H, Arendt-Nielsen L, Staahl C, et al. Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci.2005.50(11):2050-8.
[66]Arendt-Nielsen L, Bajaj P, Drewes AM. Visceral pain:gender differences in response to experimental and clinical pain. Eur J Pain.2004.8(5):465-72.
[67]· Lagergren J, Nyren O. Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients. Cancer Epidemiol Biomarkers Prev.1998.7(10):913-5.
[68]Levi F, La Vecchia C, Lucchini F, Negri E. Trends in cancer mortality sex ratios in Europe,1950-1989. World Health Stat Q.1992.45(1):117-64.
[69]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[70]Utsumi Y, Nakamura T, Nagasue N, Kubota H, Morikawa S. Role of estrogen receptors in the growth of human esophageal carcinoma. Cancer.1989.64(1):88-93.
[71]Tiffin N, Suvarna SK, Trudgill NJ, Riley SA. Sex hormone receptor immunohistochemistry staining in Barrett's oesophagus and adenocarcinoma. Histopalhology.2003.42(1):95-6.
[72]Boone J, van HR, Offerhaus GJ, van DPJ, Borel RIH, Ten KFJ. Targets for molecular therapy in esophageal squamous cell carcinoma:an immunohistochemical analysis. Dis Esophagus.2009.22(6): 496-504.
[73]Akgun H, Lechago J, Younes M. Estrogen receptor-beta is expressed in Barrett's metaplasia and associated adenocarcinoma of the esophagus. Anticancer Res.2002.22(3):1459-61.
[74]Liu L, Chirala M, Younes M. Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma. Anticancer Res.2004.24(5A):2919-24.
[75]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[76]Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K, Yasumoto K. Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus. Clin Cancer Res.2007.13(14):4046-50.
[77]Wang QM, Qi YJ, Jiang Q, Ma YF, Wang LD. Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China. Med Oncol.2011. 28(1):188-93.
[78]Wang LY. [Estrogen and progesterone receptors in esophageal carcinoma cells]. Zhonghua Zhong Liu Za Zhi.1991.13(1):23-5.
[1]Brinton RD. Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease. Adv Drug Deliv Rev.2008. 60(13-14):1504-11.
[2]Kumar DM, Simpkins JW, Agarwal N. Estrogens and neuroprotection in retinal diseases. Mol Vis.2008.14:1480-6.
[3]Hojo Y, Murakami G, Mukai H, et al. Estrogen synthesis in the brain--role in synaptic plasticity and memory. Mol Cell Endocrinol.2008.290(1-2):31-43.
[4]Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events:a meta-analysis. Eur Heart J.2008.29(16): 2031-41.
[5]Birge SJ. Hormone therapy and stroke. Clin Obstet Gynecol.2008.51(3):581-91.
[6]Deurveilher S, Cumyn EM, Peers T, Rusak B, Semba K. Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats. Am J Physiol Regul Integr Comp Physiol.2008.295(4):R1328-40.
[7]Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet Gynecol.2009.113(1):74-80.
[8]Suzuki F, Akahira J, Miura I, et al. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma. Cancer Sci.2008.99(12):2365-72.
[9]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[10]Winter DC, Taylor C, C OG, Harvey BJ. Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon. Br J Surg.2000.87(12):1684-9.
[11]Simoncini T, Genazzani AR. Non-genomic actions of sex steroid hormones. Eur J Endocrinol.2003.148(3):281-92.
[12]Moggs JG, Orphanides G. Estrogen receptors:orchestrators of pleiotropic cellular responses. EMBO Rep.2001.2(9):775-81.
[13]Alzamora R, Harvey BJ. Direct binding and activation of protein kinase C isoforms by steroid hormones. Steroids.2008.73(9-10):885-8.
[14]Muchekehu RW, Harvey BJ.17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3. Cell Calcium.2008.44(3):276-88.
[15]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[16]Ropero AB, Fuentes E, Rovira JM, Ripoll C, Soria B, Nadal A. Non-genomic actions of 17beta-oestradiol in mouse pancreatic beta-cells are mediated by a cGMP-dependent protein kinase. J Physiol.1999.521 Pt 2:397-407.
[17]Simoncini T, Varone G, Fornari L, et al. Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a fourth-generation selective estrogen receptor modulator. Endocrinology.2002.143(6):2052-61.
[18]Hennessy BA, Harvey BJ, Healy V.17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Mol Cell Endocrinol.2005.229(1-2):39-47.
[19]Available at:http://www.who.int/gender/whatisgender/en/. Accessed July 1,2011.
[20]Cancer statistics 2011. CA Cancer J Clin.Available at:http://www.cacancerjournal.com. Accessed July 1,2011.
[21]Rutegard M, Shore R, Lu Y, Lagergren P, Lindblad M. Sex differences in the incidence of gastrointestinal adenocarcinoma in Sweden 1970-2006. Eur J Cancer.2010.46(6): 1093-100.
[22]Derakhshan MH, Liptrot S, Paul J, Brown IL, Morrison D, McColl KE. Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. Gut.2009.58(1):16-23.
[23]World cancer research fund international:General world cancer statistics. Available at: http://www.wcrf.org/world_cancer_statistics.php. Accessed July 1,2011
[24]Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries,1973-1995. Int J Cancer. 2002.99(6):860-8.
[25]Rutegard M, Nordenstedt H, Lu Y, Lagergren J, Lagergren P. Sex-specific exposure prevalence of established risk factors for oesophageal adenocarcinoma. Br J Cancer.2010. 103(5):735-40.
[26]Lofdahl HE, Lu Y, Lagergren J. Sex-specific risk factor profile in oesophageal adenocarcinoma. Br J Cancer.2008.99(9):1506-10.
[27]Freedman ND, Derakhshan MH, Abnet CC, Schatzkin A, Hollenbeck AR, McColl KE. Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women. Eur J Cancer.2010.46(13):2473-8.
[28]Cheng KK, Sharp L, McKinney PA, et al. A case-control study of oesophageal adenocarcinoma in women:a preventable disease. Br J Cancer.2000.83(1):127-32.
[29]Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer.1999.83(1):18-29.
[30]Wang LD, Shi ST, Zhou Q, et al. Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. Int J Cancer.1994.59(4):514-9.
[31]Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer.2002.102(3):271-4.
[32]Holmes RS, Vaughan TL. Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol.2007.17(1):2-9.
[33]Li JY. Epidemiology of esophageal cancer in China. Natl Cancer Inst Monogr.1982.62: 113-20.
[34]Sugimachi K, Matsuoka H, Matsufuji H, Maekawa S, Kai H, Okudaira Y. Survival rates of women with carcinoma of the esophagus exceed those of men. Surg Gynecol Obstet.1987. 164(6):541-4.
[35]Micheli A, Mariotto A, Giorgi RA, Gatta G, Muti P. The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group. Eur J Cancer.1998.34(14 Spec No):2271-8.
[36]Rohatgi PR, Correa AM, Swisher SG, et al. Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation:differences in presentation and therapy outcome. Dis Esophagus.2006.19(3):152-7.
[37]Scapa E, Broide E, Waron M, Klinowski E, Eshchar J. Esophagogastric mucosal junction (EGMJ):its location as measured by endoscopy. Surg Laparosc Endosc.1997.7(2): 159-61.
[38]Li Q, Castell JA, Castell DO. Manometric determination of esophageal length. Am J Gastroenterol.1994.89(5):722-5.
[39]van HMA, Katz PO, Gideon RM, et al. Are manometric parameters of the upper esophageal sphincter and pharynx affected by age and gender. Dysphagia.2003.18(3): 211-7.
[40]McKee GJ, Johnston BT, McBride GB, Primrose WJ. Does age or sex affect pharyngeal swallowing. Clin Otolaryngol Allied Sci.1998.23(2):100-6.
[41]Vega KJ, Palacio C, Langford-Legg T, Watts J, Jamal MM. Gender variation in oesophageal motor function:analysis of 129 healthy individuals. Dig Liver Dis.2010. 42(7):482-4.
[42]COX AJ. Stomach size and its relation to chronic peptic ulcer. AMA Arch Pathol.1952. 54(5):407-22.
[43]Richter JE, Bradley LA, DeMeester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender. Dig Dis Sci.1992.37(6): 849-56.
[44]Fass R, Sampliner RE, Mackel C, McGee D, Rappaport W. Age-and gender-related differences in 24-hour esophageal pH monitoring of normal subjects. Dig Dis Sci.1993. 38(10):1926-8.
[45]Ter RB, Johnston BT, Castell DO. Influence of age and gender on gastroesophageal reflux in symptomatic patients. Dis Esophagus.1998.11(2):106-8.
[46]Rocha LP, de Melo E Silva AT, Gomes NC, et al. The influence of gender and of AIDS on the immunity of autopsied patients'esophagus. AIDS Res Hum Retroviruses.2011.27(5): 511-8.
[47]Nguyen P, Lee SD, Castell DO. Evidence of gender differences in esophageal pain threshold. Am J Gastroenterol.1995.90(6):901-5.
[48]Rao SS, Mudipalli RS, Mujica VR, Patel RS, Zimmerman B. Effects of gender and age on esophageal biomechanical properties and sensation. Am J Gastroenterol.2003.98(8): 1688-95.
[49]Reddy H, Arendt-Nielsen L, Staahl C, et al. Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci.2005.50(11): 2050-8.
[50]Arendt-Nielsen L, Bajaj P, Drewes AM. Visceral pain:gender differences in response to experimental and clinical pain. Eur J Pain.2004.8(5):465-72.
[51]Lagergren J, Nyren O. Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients. Cancer Epidemiol Biomarkers Prev.1998.7(10):913-5.
[52]Levi F, La Vecchia C, Lucchini F, Negri E. Trends in cancer mortality sex ratios in Europe, 1950-1989. World Health Stat Q.1992.45(1):117-64.
[53]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[54]Utsumi Y, Nakamura T, Nagasue N, Kubota H, Morikawa S. Role of estrogen receptors in the growth of human esophageal carcinoma. Cancer.1989.64(1):88-93.
[55]Tiffin N, Suvarna SK, Trudgill NJ, Riley SA. Sex hormone receptor immunohistochemistry staining in Barrett's oesophagus and adenocarcinoma. Histopathology 2003.42(1):95-6.
[56]Boone J, van HR, Offerhaus GJ, van DPJ, Borel RIH, Ten KFJ. Targets for molecular therapy in esophageal squamous cell carcinoma:an immunohistochemical analysis. Dis Esophagus.2009.22(6):496-504.
[57]Akgun H, Lechago J, Younes M. Estrogen receptor-beta is expressed in Barrett's metaplasia and associated adenocarcinoma of the esophagus. Anticancer Res.2002.22(3): 1459-61.
[58]Liu L, Chirala M, Younes M. Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma. Anticancer Res.2004.24(5A): 2919-24.
[59]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[60]Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K, Yasumoto K. Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus. Clin Cancer Res.2007.13(14):4046-50.
[61]Wang QM, Qi YJ, Jiang Q, Ma YF, Wang LD. Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China. Med Oncol.2011.28(1):188-93.
[62]Wang LY. [Estrogen and progesterone receptors in esophageal carcinoma cells]. Zhonghua Zhong Liu Za Zhi.1991.13(1):23-5.
[63]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J Clin. 2005.55(2):74-108.
[64]Sipponen P, Correa P. Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern:etiologic hypothesis. Gastric Cancer.2002.5(4):213-9.
[65]Kominea A, Konstantinopoulos PA, Kapranos N, et al. Androgen receptor (AR) expression is an independent unfavorable prognostic factor in gastric cancer. J Cancer Res Clin Oncol. 2004.130(5):253-8.
[66]Takano N, Iizuka N, Hazama S, Yoshino S, Tangoku A, Oka M. Expression of estrogen receptor-alpha and-beta mRNAs in human gastric cancer. Cancer Lett.2002.176(2): 129-35.
[67]Freedman ND, Chow WH, Gao YT, et al. Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women. Gut.2007.56(12):1671-7.
[68]Frise S, Kreiger N, Gallinger S, Tomlinson G, Cotterchio M. Menstrual and reproductive risk factors and risk for gastric adenocarcinoma in women:findings from the Canadian national enhanced cancer surveillance system. Ann Epidemiol.2006.16(12):908-16.
[69]Heuch I, Kvale G. Menstrual and reproductive factors and risk of gastric cancer:a Norwegian cohort study. Cancer Causes Control.2000.11(9):869-74.
[70]Inoue M, Ito LS, Tajima K, et al. Height, weight, menstrual and reproductive factors and risk of gastric cancer among Japanese postmenopausal women:analysis by subsite and histologic subtype. Int J Cancer.2002.97(6):833-8.
[71]Kaneko S, Tamakoshi A, Ohno Y, Mizoue T, Yoshimura T. Menstrual and reproductive factors and the mortality risk of gastric cancer in Japanese menopausal females. Cancer Causes Control.2003.14(1):53-9.
[72]La Vecchia C, D'Avanzo B, Franceschi S, Negri E, Parazzini F, Decarli A. Menstrual and reproductive factors and gastric-cancer risk in women. Int J Cancer.1994.59(6):761-4.
[73]Lindblad M, Garcia RLA, Chandanos E, Lagergren J. Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas. Br J Cancer.2006.94(1):136-41.
[74]Palli D, Cipriani F, Decarli A, et al. Reproductive history and gastric cancer among post-menopausal women. Int J Cancer.1994.56(6):812-5.
[75]Lindblad M, Ye W, Rubio C, Lagergren J. Estrogen and risk of gastric cancer:a protective effect in a nationwide cohort study of patients with prostate cancer in Sweden. Cancer Epidemiol Biomarkers Prev.2004.13(12):2203-7.
[76]Matsuyama Y, Tominaga T, Nomura Y, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann Oncol.2000.11(12):1537-43.
[77]Rutqvist LE, Johansson H, Signomklao T, Johansson U, Fornander T, Wilking N. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group. J Natl Cancer Inst.1995.87(9):645-51.
[78]Furukawa H, Iwanaga T, Koyama H, Taniguchi H. Effect of sex hormones on carcinogenesis in the stomachs of rats. Cancer Res.1982.42(12):5181-2.
[79]Ohtani M, Garcia A, Rogers AB, et al. Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. Carcinogenesis.2007.28(12):2597-604.
[80]Sharp L, Cardy AH, Cotton SC, Little J. CYP17 gene polymorphisms:prevalence and associations with hormone levels and related factors, a HuGE review. Am J Epidemiol. 2004.160(8):729-40.
[81]Tsuchiya Y, Nakajima M, Yokoi T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett.2005.227(2):115-24.
[82]Hammond GL. Potential functions of plasma steroid-binding proteins. Trends Endocrinol Metab.1995.6(9-10):298-304.
[83]Yue W, Santen RJ, Wang JP, et al. Genotoxic metabolites of estradiol in breast:potential mechanism of estradiol induced carcinogenesis. J Steroid Biochem Mol Biol.2003. 86(3-5):477-86.
[84]Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells:review and perspectives. Carcinogenesis.1998.19(1):1-27.
[85]Freedman ND, Ahn J, Hou L, et al. Polymorphisms in estrogen-and androgen-metabolizing genes and the risk of gastric cancer. Carcinogenesis.2009.30(1):71-7.
[86]Jemal A, Siegel R, Ward E, et al. Cancer statistics,2008. CA Cancer J Clin.2008.58(2): 71-96.
[87]Khan ZR, Neugut Al, Ahsan H, Chabot JA. Risk factors for biliary tract cancers. Am J Gastroenterol.1999.94(1):149-52.
[88]Zatonski WA, Lowenfels AB, Boyle P, et al. Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer. J Natl Cancer Inst.1997.89(15):1132-8.
[89]Hsing AW, Gao YT, Han TQ, et al. Gallstones and the risk of biliary tract cancer:a population-based study in China. Br J Cancer.2007.97(11):1577-82.
[90]Curtis HS, Couse JF, Korach KS. Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice:what their phenotypes reveal about mechanisms of estrogen action. Breast Cancer Res.2000.2(5):345-52.
[91]Oettel M. Is there a role for estrogens in the maintenance of men's health. Aging Male. 2002.5(4):248-57.
[92]Nakamura S, Muro H, Suzuki S. Estrogen and progesterone receptors in gallbladder cancer. Jpn J Surg.1989.19(2):189-94.
[93]Park SK, Andreotti G Rashid A, et al. Polymorphisms of estrogen receptors and risk of biliary tract cancers and gallstones:a population-based study in Shanghai, China. Carcinogenesis.2010.31(5):842-6.
[94]Farquhar CM, Marjoribanks J, Lethaby A, Lamberts Q, Suckling JA. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2005. (3):CD004143.
[95]Nelson RL, Dollear T, Freels S, Persky V. The relation of age, race, and gender to the subsite location of colorectal carcinoma. Cancer.1997.80(2):193-7.
[96]Brenner H, Hoffmeister M, Arndt V, Haug U. Gender differences in colorectal cancer: implications for age at initiation of screening. Br J Cancer.2007.96(5):828-31.
[97]Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med.1995. 122(5):327-34.
[98]Howard RA, Freedman DM, Park Y, Hollenbeck A, Schatzkin A, Leitzmann MF. Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study. Cancer Causes Control.2008.19(9):939-53.
[99]Ashktorab H, Smoot DT, Carethers JM, et al. High incidence of microsatellite instability in colorectal cancer from African Americans. Clin Cancer Res.2003.9(3):1112-7.
[100]Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet.2000. 355(9217):1745-50.
[101]Ries LA, Wingo PA, Miller DS, et al. The annual report to the nation on the status of cancer,1973-1997, with a special section on colorectal cancer. Cancer.2000.88(10):2398-424.
[102]Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women:principal results From the Women's Health Initiative randomized controlled trial. JAMA.2002.288(3):321-33.
[103]Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med.2004.350(10):991-1004.
[104]Newcomb PA, Storer BE. Postmenopausal hormone use and risk of large-bowel cancer. J Natl Cancer Inst.1995.87(14):1067-71.
[105]Mandelson MT, Miglioretti D, Newcomb PA, Harrison R, Potter JD. Hormone replacement therapy in relation to survival in women diagnosed with colon cancer. Cancer Causes Control.2003.14(10):979-84.
[106]Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives:cohort data from the Royal College of General Practitioner's oral contraception study. BMJ.2007.335(7621):651.
[107]Fernandez E, La Vecchia C, Balducci A, Chatenoud L, Franceschi S, Negri E. Oral contraceptives and colorectal cancer risk:a meta-analysis. Br J Cancer.2001.84(5):722-7.
[108]Franceschi S, Gallus S, Talamini R, Tavani A, Negri E, La Vecchia C. Menopause and colorectal cancer. Br J Cancer.2000.82(11):1860-2.
[109]Zhang W, Press OA, Haiman CA, et al. Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. J Clin Oncol.2007.25(24):3726-31.
[110]Press OA, Zhang W, Gordon MA, et al. Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer. Cancer Res.2008.68(8):3037-42.
[111]Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol.2002.20(6):1491-8.
[112]Woods SE, Basho S, Engel A. The influence of gender on colorectal cancer stage:the state of Ohio,1996-2001. J Womens Health (Larchmt).2006.15(7):877-81.
[113]McArdle CS, McMillan DC, Hole DJ. Male gender adversely affects survival following surgery for colorectal cancer. Br J Surg.2003.90(6):711-5.
[114]Wichmann MW, Muller C, Hornung HM, Lau-Werner U, Schildberg FW. Gender differences in long-term survival of patients with colorectal cancer. Br J Surg.2001.88(8): 1092-8.
[115]Koo JH, Jalaludin B, Wong SK, Kneebone A, Connor SJ, Leong RW. Improved survival in young women with colorectal cancer. Am J Gastroenterol.2008.103(6):1488-95.
[116]Angell-Andersen E, Tretli S, Coleman MP, Langmark F, Grotmol T. Colorectal cancer survival trends in Norway 1958-1997. Eur J Cancer.2004.40(5):734-42.
[117]Sica V, Nola E, Contieri E, et al. Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res.1984.44(10):4670-4.
[118]Enmark E, Pelto-Huikko M, Grandien K, et al. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997.82(12):4258-65.
[119]Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW. Selective loss of estrogen receptor beta in malignant human colon. Cancer Res.2000.60(2):245-8.
[120]Qiu Y, Waters CE, Lewis AE, Langman MJ, Eggo MC. Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta. J Endocrinol.2002.174(3):369-77.
[121]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[122]Martineti V, Picariello L, Tognarini I, et al. ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr Relat Cancer.2005.12(2):455-69.
[123]Xie LQ, Yu JP, Luo HS. Expression of estrogen receptor beta in human colorectal cancer. World J Gastroenterol.2004.10(2):214-7.
[124]Hsu HH, Cheng SF, Wu CC, et al. Apoptotic effects of over-expressed estrogen receptor-beta on LoVo colon cancer cell is mediated by p53 signalings in a ligand-dependent manner. Chin J Physiol.2006.49(2):110-6.
[125]Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics.2006.7(8):497-508.
[126]Galluzzo P, Caiazza F, Moreno S, Marino M. Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr Relat Cancer.2007.14(1): 153-67.
[127]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[128]Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol.2006.20(9):1996-2009.
[129]Marino M, Galluzzo P, Leone S, Acconcia F, Ascenzi P. Nitric oxide impairs the 17beta-estradiol-induced apoptosis in human colon adenocarcinoma cells. Endocr Relat Cancer.2006.13(2):559-69.
[130]Gilad LA, Schwartz B. Association of estrogen receptor beta with plasma-membrane caveola components:implication in control of vitamin D receptor. J Mol Endocrinol.2007. 38(6):603-18.
[131]Caiazza F, Galluzzo P, Lorenzetti S, Marino M.17Beta-estradiol induces ERbeta up-regulation via p38/MAPK activation in colon cancer cells. Biochem Biophys Res Commun. 2007.359(1):102-7.
[2]Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer.2002.102(3):271-4.
[3]王立东.河南食管癌研究的理解和思考.郑州大学学报：医学学版.2006.41(1)：1-5.
[4]Wang LD, Hong JY, Qiu SL, Gao H, Yang CS. Accumulation of p53 protein in human esophageal precancerous lesions:a possible early biomarker for carcinogenesis. Cancer Res.1993.53(8):1783-7.
[5]Wang LD, Zhou Q, Yang CS. Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area. J Cell Biochem Suppl.1997.28-29:159-65.
[6]Correa P. Precursors of gastric and esophageal cancer. Cancer.1982.50(11 Suppl):2554-65.
[7]杜百廉主编.食管癌.1994.30-107.
[8]Zhang W, Press OA, Haiman CA, et al. Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. J Clin Oncol.2007. 25(24):3726-31.
[9]李光恒.食管／贲门癌家族性与保护人群(山西阳城肿瘤防治点调查报告).肿瘤防治研究.1980.2(6)：1-6.
[10]Parkin DM LE, Muir CS. Estimate of the worldwide frequency of sixteen major cancers in 1980. In J Cancer.1988.41(2):184-197.
[11]李卫东,张春林.山西省阳泉市部分人口食管癌遗传流行病学调查.中华医学杂志.1998.78(3)：203-206.
[12]Gao Y, Hu N, Han X, et al. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China. BMC Cancer.2009.9:269.
[13]Liu M, Su M, Tian DP, Zhang GH, Yang HL, Gao YX. Heredity, diet and lifestyle as determining risk factors for the esophageal cancer on Nanao Island in Southern China. Fam Cancer.2010.9(2):229-38.
[14]Wen D, Wang S, Zhang L, Wei L, Zhou W, Peng Q. Early onset, multiple primary malignancies, and poor prognosis are indicative of an inherited predisposition to esophageal squamous cell carcinoma for the familial as opposed to the sporadic cases--an update on over 14-year survival. Eur J Med Genet.2009. 52(6):381-5.
[15]王立东[1],樊慧[1],焦新英[2]等.河南食管癌高发区95对单卵双胞胎疾病谱和2323例食管癌患者家族史调查.中华肿瘤防治杂志.2006.13(20)：1521-1524.
[16]Available at:http://www.who.int/gender/whatisgender/en/. Accessed July 1,2011.
[17]Cancer statistics 2011. CA Cancer J Clin.Available at:http://www.cacancerjournal.com. Accessed July 1, 2011.
[18]Rutegard M, Shore R, Lu Y, Lagergren P, Lindblad M. Sex differences in the incidence of gastrointestinal adenocarcinoma in Sweden 1970-2006. Eur J Cancer.2010.46(6):1093-100.
[19]Derakhshan MH, Liptrot S, Paul J, Brown IL, Morrison D, McColl K.E. Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. Gut.2009.58(1):16-23.
[20]World cancer research fund international:General world cancer statistics. Available at: http://www.wcrf.org/world_cancer_statistics.php. Accessed July 1,2011.
[21]Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries,1973-1995. Int J Cancer.2002.99(6):860-8.
[22]Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer.1999.83(1):18-29.
[23]Wang LD, Shi ST, Zhou Q, et al. Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. Int J Cancer.1994.59(4):514-9.
[24]Holmes RS, Vaughan TL. Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol.2007. 17(1):2-9.
[25]Li JY. Epidemiology of esophageal cancer in China. Natl Cancer Inst Monogr.1982.62:113-20.
[26]Sugimachi K, Matsuoka H, Matsufuji H, Maekawa S, Kai H, Okudaira Y. Survival rates of women with carcinoma of the esophagus exceed those of men. Surg Gynecol Obstet.1987.164(6):541-4.
[27]Micheli A, Mariotto A, Giorgi RA, Gatta G, Muti P. The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group. Eur J Cancer.1998.34(14 Spec No):2271-8.
[28]Rohatgi PR, Correa AM, Swisher SG, et al. Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation:differences in presentation and therapy outcome. Dis Esophagus. 2006.19(3):152-7.
[29]杨科,崔树德,李连方.乳腺癌组织中ER. PR、Ps2、C-erbB-2表达与新辅助化疗疗效的关系.山东医药.2011.51(6)：18-19.
[30]Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science.2001.291(5507): 1304-51.
[31]Brinton RD. Estrogen regulation of glucose metabolism and mitochondrial function:therapeutic implications for prevention of Alzheimer's disease. Adv Drug Deliv Rev.2008.60(13-14):1504-11.
[32]Kumar DM, Simpkins JW, Agarwal N. Estrogens and neuroprotection in retinal diseases. Mol Vis.2008. 14:1480-6.
[33]Hojo Y, Murakami G, Mukai H, et al. Estrogen synthesis in the brain--role in synaptic plasticity and memory. Mol Cell Endocrinol.2008.290(1-2):31-43.
[34]Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events:a meta-analysis. Eur Heart J.2008.29(16):2031-41.
[35]Birge SJ. Hormone therapy and stroke. Clin Obstet Gynecol.2008.51(3):581-91.
[36]Deurveilher S, Cumyn EM, Peers T, Rusak B, Semba K. Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats. Am J Physiol Regul Integr Comp Physiol.2008.295(4):R1328-40.
[37]Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet Gynecol.2009.113(1):74-80.
[38]Suzuki F, Akahira J, Miura I, et al. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma. Cancer Sci.2008.99(12):2365-72.
[39]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[40]Winter DC, Taylor C, C OG, Harvey BJ. Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon. Br J Surg.2000.87(12):1684-9.
[41]Simoncini T, Genazzani AR. Non-genomic actions of sex steroid hormones. Eur J Endocrinol.2003. 148(3):281-92.
[42]Moggs JG, Orphanides G. Estrogen receptors:orchestrators of pleiotropic cellular responses. EMBO Rep. 2001.2(9):775-81.
[43]Alzamora R, Harvey BJ. Direct binding and activation of protein kinase C isoforms by steroid hormones. Steroids.2008.73(9-10):885-8.
[44]Muchekehu RW, Harvey BJ.17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3. Cell Calcium.2008.44(3):276-88.
[45]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[46]Ropero AB, Fuentes E, Rovira JM, Ripoll C, Soria B, Nadal A. Non-genomic actions of 17beta-oestradiol in mouse pancreatic beta-cells are mediated by a cGMP-dependent protein kinase. J Physiol.1999.521 Pt 2:397-407.
[47]Simoncini T, Varone G, Fornari L, et al. Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a.fourth-generation selective estrogen receptor modulator. Endocrinology.2002.143(6):2052-61.
[48]Hennessy BA, Harvey BJ, Healy V.17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Mol Cell Endocrinol.2005.229(1-2):39-47.
[49]Rutegard M, Nordenstedt H, Lu Y, Lagergren J, Lagergren P. Sex-specific exposure prevalence of established risk factors for oesophageal adenocarcinoma. Br J Cancer.2010.103(5):735-40.
[50]Lofdahl HE, Lu Y, Lagergren J. Sex-specific risk factor profile in oesophageal adenocarcinoma. Br J Cancer.2008.99(9):1506-10.
[51]Freedman ND, Derakhshan MH, Abnet CC, Schatzkin A, Hollenbeck AR, McColl KE. Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women. Eur J Cancer.2010.46(13):2473-8.
[52]Cheng KK, Sharp L, McKinney PA, et al. A case-control study of oesophageal adenocarcinoma in women: a preventable disease. Br J Cancer.2000.83(1):127-32.
[53]Scapa E, Broide E, Waron M, Klinowski E, Eshchar J. Esophagogastric mucosal junction (EGMJ):its location as measured by endoscopy. Surg Laparosc Endosc.1997.7(2):159-61.
[54]Li Q, Castell JA, Castell DO. Manometric determination of esophageal length. Am J Gastroenterol.1994. 89(5):722-5.
[55]van HMA, Katz PO, Gideon RM, et al. Are manometric parameters of the upper esophageal sphincter and pharynx affected by age and gender. Dysphagia.2003.18(3):211-7.
[56]McKee GJ, Johnston BT, McBride GB, Primrose WJ. Does age or sex affect pharyngeal swallowing. Clin Otolaryngol Allied Sci.1998.23(2):100-6.
[57]Vega KJ, Palacio C, Langford-Legg T, Watts J, Jamal MM. Gender variation in oesophageal motor function:analysis of 129 healthy individuals. Dig Liver Dis.2010.42(7):482-4.
[58]COX AJ. Stomach size and its relation to chronic peptic ulcer. AMA Arch Pathol.1952.54(5):407-22.
[59]Richter JE, Bradley LA, DeMeester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender. Dig Dis Sci.1992.37(6):849-56.
[60]Fass R, Sampliner RE, Mackel C, McGee D, Rappaport W. Age-and gender-related differences in 24-hour esophageal pH monitoring of normal subjects. Dig Dis Sci.1993.38(10):1926-8.
[61]Ter RB, Johnston BT, Castell DO. Influence of age and gender on gastroesophageal reflux in symptomatic patients. Dis Esophagus.1998.11(2):106-8.
[62]Rocha LP, de Melo E Silva AT, Gomes NC, et al. The influence of gender and of AIDS on the immunity of autopsied patients'esophagus. AIDS Res Hum Retroviruses.2011.27(5):511-8.
[63]Nguyen P, Lee SD, Castell DO. Evidence of gender differences in esophageal pain threshold. Am J Gastroenterol.1995.90(6):901-5.
[64]Rao SS, Mudipalli RS, Mujica VR, Patel RS, Zimmerman B. Effects of gender and age on esophageal biomechanical properties and sensation. Am J Gastroenterol.2003.98(8):1688-95.
[65]Reddy H, Arendt-Nielsen L, Staahl C, et al. Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci.2005.50(11):2050-8.
[66]Arendt-Nielsen L, Bajaj P, Drewes AM. Visceral pain:gender differences in response to experimental and clinical pain. Eur J Pain.2004.8(5):465-72.
[67]· Lagergren J, Nyren O. Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients. Cancer Epidemiol Biomarkers Prev.1998.7(10):913-5.
[68]Levi F, La Vecchia C, Lucchini F, Negri E. Trends in cancer mortality sex ratios in Europe,1950-1989. World Health Stat Q.1992.45(1):117-64.
[69]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[70]Utsumi Y, Nakamura T, Nagasue N, Kubota H, Morikawa S. Role of estrogen receptors in the growth of human esophageal carcinoma. Cancer.1989.64(1):88-93.
[71]Tiffin N, Suvarna SK, Trudgill NJ, Riley SA. Sex hormone receptor immunohistochemistry staining in Barrett's oesophagus and adenocarcinoma. Histopalhology.2003.42(1):95-6.
[72]Boone J, van HR, Offerhaus GJ, van DPJ, Borel RIH, Ten KFJ. Targets for molecular therapy in esophageal squamous cell carcinoma:an immunohistochemical analysis. Dis Esophagus.2009.22(6): 496-504.
[73]Akgun H, Lechago J, Younes M. Estrogen receptor-beta is expressed in Barrett's metaplasia and associated adenocarcinoma of the esophagus. Anticancer Res.2002.22(3):1459-61.
[74]Liu L, Chirala M, Younes M. Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma. Anticancer Res.2004.24(5A):2919-24.
[75]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[76]Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K, Yasumoto K. Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus. Clin Cancer Res.2007.13(14):4046-50.
[77]Wang QM, Qi YJ, Jiang Q, Ma YF, Wang LD. Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China. Med Oncol.2011. 28(1):188-93.
[78]Wang LY. [Estrogen and progesterone receptors in esophageal carcinoma cells]. Zhonghua Zhong Liu Za Zhi.1991.13(1):23-5.
[1]Brinton RD. Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease. Adv Drug Deliv Rev.2008. 60(13-14):1504-11.
[2]Kumar DM, Simpkins JW, Agarwal N. Estrogens and neuroprotection in retinal diseases. Mol Vis.2008.14:1480-6.
[3]Hojo Y, Murakami G, Mukai H, et al. Estrogen synthesis in the brain--role in synaptic plasticity and memory. Mol Cell Endocrinol.2008.290(1-2):31-43.
[4]Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events:a meta-analysis. Eur Heart J.2008.29(16): 2031-41.
[5]Birge SJ. Hormone therapy and stroke. Clin Obstet Gynecol.2008.51(3):581-91.
[6]Deurveilher S, Cumyn EM, Peers T, Rusak B, Semba K. Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats. Am J Physiol Regul Integr Comp Physiol.2008.295(4):R1328-40.
[7]Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet Gynecol.2009.113(1):74-80.
[8]Suzuki F, Akahira J, Miura I, et al. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma. Cancer Sci.2008.99(12):2365-72.
[9]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[10]Winter DC, Taylor C, C OG, Harvey BJ. Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon. Br J Surg.2000.87(12):1684-9.
[11]Simoncini T, Genazzani AR. Non-genomic actions of sex steroid hormones. Eur J Endocrinol.2003.148(3):281-92.
[12]Moggs JG, Orphanides G. Estrogen receptors:orchestrators of pleiotropic cellular responses. EMBO Rep.2001.2(9):775-81.
[13]Alzamora R, Harvey BJ. Direct binding and activation of protein kinase C isoforms by steroid hormones. Steroids.2008.73(9-10):885-8.
[14]Muchekehu RW, Harvey BJ.17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3. Cell Calcium.2008.44(3):276-88.
[15]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[16]Ropero AB, Fuentes E, Rovira JM, Ripoll C, Soria B, Nadal A. Non-genomic actions of 17beta-oestradiol in mouse pancreatic beta-cells are mediated by a cGMP-dependent protein kinase. J Physiol.1999.521 Pt 2:397-407.
[17]Simoncini T, Varone G, Fornari L, et al. Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a fourth-generation selective estrogen receptor modulator. Endocrinology.2002.143(6):2052-61.
[18]Hennessy BA, Harvey BJ, Healy V.17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Mol Cell Endocrinol.2005.229(1-2):39-47.
[19]Available at:http://www.who.int/gender/whatisgender/en/. Accessed July 1,2011.
[20]Cancer statistics 2011. CA Cancer J Clin.Available at:http://www.cacancerjournal.com. Accessed July 1,2011.
[21]Rutegard M, Shore R, Lu Y, Lagergren P, Lindblad M. Sex differences in the incidence of gastrointestinal adenocarcinoma in Sweden 1970-2006. Eur J Cancer.2010.46(6): 1093-100.
[22]Derakhshan MH, Liptrot S, Paul J, Brown IL, Morrison D, McColl KE. Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. Gut.2009.58(1):16-23.
[23]World cancer research fund international:General world cancer statistics. Available at: http://www.wcrf.org/world_cancer_statistics.php. Accessed July 1,2011
[24]Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries,1973-1995. Int J Cancer. 2002.99(6):860-8.
[25]Rutegard M, Nordenstedt H, Lu Y, Lagergren J, Lagergren P. Sex-specific exposure prevalence of established risk factors for oesophageal adenocarcinoma. Br J Cancer.2010. 103(5):735-40.
[26]Lofdahl HE, Lu Y, Lagergren J. Sex-specific risk factor profile in oesophageal adenocarcinoma. Br J Cancer.2008.99(9):1506-10.
[27]Freedman ND, Derakhshan MH, Abnet CC, Schatzkin A, Hollenbeck AR, McColl KE. Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women. Eur J Cancer.2010.46(13):2473-8.
[28]Cheng KK, Sharp L, McKinney PA, et al. A case-control study of oesophageal adenocarcinoma in women:a preventable disease. Br J Cancer.2000.83(1):127-32.
[29]Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer.1999.83(1):18-29.
[30]Wang LD, Shi ST, Zhou Q, et al. Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. Int J Cancer.1994.59(4):514-9.
[31]Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer.2002.102(3):271-4.
[32]Holmes RS, Vaughan TL. Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol.2007.17(1):2-9.
[33]Li JY. Epidemiology of esophageal cancer in China. Natl Cancer Inst Monogr.1982.62: 113-20.
[34]Sugimachi K, Matsuoka H, Matsufuji H, Maekawa S, Kai H, Okudaira Y. Survival rates of women with carcinoma of the esophagus exceed those of men. Surg Gynecol Obstet.1987. 164(6):541-4.
[35]Micheli A, Mariotto A, Giorgi RA, Gatta G, Muti P. The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group. Eur J Cancer.1998.34(14 Spec No):2271-8.
[36]Rohatgi PR, Correa AM, Swisher SG, et al. Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation:differences in presentation and therapy outcome. Dis Esophagus.2006.19(3):152-7.
[37]Scapa E, Broide E, Waron M, Klinowski E, Eshchar J. Esophagogastric mucosal junction (EGMJ):its location as measured by endoscopy. Surg Laparosc Endosc.1997.7(2): 159-61.
[38]Li Q, Castell JA, Castell DO. Manometric determination of esophageal length. Am J Gastroenterol.1994.89(5):722-5.
[39]van HMA, Katz PO, Gideon RM, et al. Are manometric parameters of the upper esophageal sphincter and pharynx affected by age and gender. Dysphagia.2003.18(3): 211-7.
[40]McKee GJ, Johnston BT, McBride GB, Primrose WJ. Does age or sex affect pharyngeal swallowing. Clin Otolaryngol Allied Sci.1998.23(2):100-6.
[41]Vega KJ, Palacio C, Langford-Legg T, Watts J, Jamal MM. Gender variation in oesophageal motor function:analysis of 129 healthy individuals. Dig Liver Dis.2010. 42(7):482-4.
[42]COX AJ. Stomach size and its relation to chronic peptic ulcer. AMA Arch Pathol.1952. 54(5):407-22.
[43]Richter JE, Bradley LA, DeMeester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender. Dig Dis Sci.1992.37(6): 849-56.
[44]Fass R, Sampliner RE, Mackel C, McGee D, Rappaport W. Age-and gender-related differences in 24-hour esophageal pH monitoring of normal subjects. Dig Dis Sci.1993. 38(10):1926-8.
[45]Ter RB, Johnston BT, Castell DO. Influence of age and gender on gastroesophageal reflux in symptomatic patients. Dis Esophagus.1998.11(2):106-8.
[46]Rocha LP, de Melo E Silva AT, Gomes NC, et al. The influence of gender and of AIDS on the immunity of autopsied patients'esophagus. AIDS Res Hum Retroviruses.2011.27(5): 511-8.
[47]Nguyen P, Lee SD, Castell DO. Evidence of gender differences in esophageal pain threshold. Am J Gastroenterol.1995.90(6):901-5.
[48]Rao SS, Mudipalli RS, Mujica VR, Patel RS, Zimmerman B. Effects of gender and age on esophageal biomechanical properties and sensation. Am J Gastroenterol.2003.98(8): 1688-95.
[49]Reddy H, Arendt-Nielsen L, Staahl C, et al. Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci.2005.50(11): 2050-8.
[50]Arendt-Nielsen L, Bajaj P, Drewes AM. Visceral pain:gender differences in response to experimental and clinical pain. Eur J Pain.2004.8(5):465-72.
[51]Lagergren J, Nyren O. Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients. Cancer Epidemiol Biomarkers Prev.1998.7(10):913-5.
[52]Levi F, La Vecchia C, Lucchini F, Negri E. Trends in cancer mortality sex ratios in Europe, 1950-1989. World Health Stat Q.1992.45(1):117-64.
[53]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[54]Utsumi Y, Nakamura T, Nagasue N, Kubota H, Morikawa S. Role of estrogen receptors in the growth of human esophageal carcinoma. Cancer.1989.64(1):88-93.
[55]Tiffin N, Suvarna SK, Trudgill NJ, Riley SA. Sex hormone receptor immunohistochemistry staining in Barrett's oesophagus and adenocarcinoma. Histopathology 2003.42(1):95-6.
[56]Boone J, van HR, Offerhaus GJ, van DPJ, Borel RIH, Ten KFJ. Targets for molecular therapy in esophageal squamous cell carcinoma:an immunohistochemical analysis. Dis Esophagus.2009.22(6):496-504.
[57]Akgun H, Lechago J, Younes M. Estrogen receptor-beta is expressed in Barrett's metaplasia and associated adenocarcinoma of the esophagus. Anticancer Res.2002.22(3): 1459-61.
[58]Liu L, Chirala M, Younes M. Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma. Anticancer Res.2004.24(5A): 2919-24.
[59]Kalayarasan R, Ananthakrishnan N, Kate V, Basu D. Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus.2008.21(4):298-303.
[60]Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K, Yasumoto K. Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus. Clin Cancer Res.2007.13(14):4046-50.
[61]Wang QM, Qi YJ, Jiang Q, Ma YF, Wang LD. Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China. Med Oncol.2011.28(1):188-93.
[62]Wang LY. [Estrogen and progesterone receptors in esophageal carcinoma cells]. Zhonghua Zhong Liu Za Zhi.1991.13(1):23-5.
[63]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J Clin. 2005.55(2):74-108.
[64]Sipponen P, Correa P. Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern:etiologic hypothesis. Gastric Cancer.2002.5(4):213-9.
[65]Kominea A, Konstantinopoulos PA, Kapranos N, et al. Androgen receptor (AR) expression is an independent unfavorable prognostic factor in gastric cancer. J Cancer Res Clin Oncol. 2004.130(5):253-8.
[66]Takano N, Iizuka N, Hazama S, Yoshino S, Tangoku A, Oka M. Expression of estrogen receptor-alpha and-beta mRNAs in human gastric cancer. Cancer Lett.2002.176(2): 129-35.
[67]Freedman ND, Chow WH, Gao YT, et al. Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women. Gut.2007.56(12):1671-7.
[68]Frise S, Kreiger N, Gallinger S, Tomlinson G, Cotterchio M. Menstrual and reproductive risk factors and risk for gastric adenocarcinoma in women:findings from the Canadian national enhanced cancer surveillance system. Ann Epidemiol.2006.16(12):908-16.
[69]Heuch I, Kvale G. Menstrual and reproductive factors and risk of gastric cancer:a Norwegian cohort study. Cancer Causes Control.2000.11(9):869-74.
[70]Inoue M, Ito LS, Tajima K, et al. Height, weight, menstrual and reproductive factors and risk of gastric cancer among Japanese postmenopausal women:analysis by subsite and histologic subtype. Int J Cancer.2002.97(6):833-8.
[71]Kaneko S, Tamakoshi A, Ohno Y, Mizoue T, Yoshimura T. Menstrual and reproductive factors and the mortality risk of gastric cancer in Japanese menopausal females. Cancer Causes Control.2003.14(1):53-9.
[72]La Vecchia C, D'Avanzo B, Franceschi S, Negri E, Parazzini F, Decarli A. Menstrual and reproductive factors and gastric-cancer risk in women. Int J Cancer.1994.59(6):761-4.
[73]Lindblad M, Garcia RLA, Chandanos E, Lagergren J. Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas. Br J Cancer.2006.94(1):136-41.
[74]Palli D, Cipriani F, Decarli A, et al. Reproductive history and gastric cancer among post-menopausal women. Int J Cancer.1994.56(6):812-5.
[75]Lindblad M, Ye W, Rubio C, Lagergren J. Estrogen and risk of gastric cancer:a protective effect in a nationwide cohort study of patients with prostate cancer in Sweden. Cancer Epidemiol Biomarkers Prev.2004.13(12):2203-7.
[76]Matsuyama Y, Tominaga T, Nomura Y, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann Oncol.2000.11(12):1537-43.
[77]Rutqvist LE, Johansson H, Signomklao T, Johansson U, Fornander T, Wilking N. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group. J Natl Cancer Inst.1995.87(9):645-51.
[78]Furukawa H, Iwanaga T, Koyama H, Taniguchi H. Effect of sex hormones on carcinogenesis in the stomachs of rats. Cancer Res.1982.42(12):5181-2.
[79]Ohtani M, Garcia A, Rogers AB, et al. Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. Carcinogenesis.2007.28(12):2597-604.
[80]Sharp L, Cardy AH, Cotton SC, Little J. CYP17 gene polymorphisms:prevalence and associations with hormone levels and related factors, a HuGE review. Am J Epidemiol. 2004.160(8):729-40.
[81]Tsuchiya Y, Nakajima M, Yokoi T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett.2005.227(2):115-24.
[82]Hammond GL. Potential functions of plasma steroid-binding proteins. Trends Endocrinol Metab.1995.6(9-10):298-304.
[83]Yue W, Santen RJ, Wang JP, et al. Genotoxic metabolites of estradiol in breast:potential mechanism of estradiol induced carcinogenesis. J Steroid Biochem Mol Biol.2003. 86(3-5):477-86.
[84]Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells:review and perspectives. Carcinogenesis.1998.19(1):1-27.
[85]Freedman ND, Ahn J, Hou L, et al. Polymorphisms in estrogen-and androgen-metabolizing genes and the risk of gastric cancer. Carcinogenesis.2009.30(1):71-7.
[86]Jemal A, Siegel R, Ward E, et al. Cancer statistics,2008. CA Cancer J Clin.2008.58(2): 71-96.
[87]Khan ZR, Neugut Al, Ahsan H, Chabot JA. Risk factors for biliary tract cancers. Am J Gastroenterol.1999.94(1):149-52.
[88]Zatonski WA, Lowenfels AB, Boyle P, et al. Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer. J Natl Cancer Inst.1997.89(15):1132-8.
[89]Hsing AW, Gao YT, Han TQ, et al. Gallstones and the risk of biliary tract cancer:a population-based study in China. Br J Cancer.2007.97(11):1577-82.
[90]Curtis HS, Couse JF, Korach KS. Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice:what their phenotypes reveal about mechanisms of estrogen action. Breast Cancer Res.2000.2(5):345-52.
[91]Oettel M. Is there a role for estrogens in the maintenance of men's health. Aging Male. 2002.5(4):248-57.
[92]Nakamura S, Muro H, Suzuki S. Estrogen and progesterone receptors in gallbladder cancer. Jpn J Surg.1989.19(2):189-94.
[93]Park SK, Andreotti G Rashid A, et al. Polymorphisms of estrogen receptors and risk of biliary tract cancers and gallstones:a population-based study in Shanghai, China. Carcinogenesis.2010.31(5):842-6.
[94]Farquhar CM, Marjoribanks J, Lethaby A, Lamberts Q, Suckling JA. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2005. (3):CD004143.
[95]Nelson RL, Dollear T, Freels S, Persky V. The relation of age, race, and gender to the subsite location of colorectal carcinoma. Cancer.1997.80(2):193-7.
[96]Brenner H, Hoffmeister M, Arndt V, Haug U. Gender differences in colorectal cancer: implications for age at initiation of screening. Br J Cancer.2007.96(5):828-31.
[97]Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med.1995. 122(5):327-34.
[98]Howard RA, Freedman DM, Park Y, Hollenbeck A, Schatzkin A, Leitzmann MF. Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study. Cancer Causes Control.2008.19(9):939-53.
[99]Ashktorab H, Smoot DT, Carethers JM, et al. High incidence of microsatellite instability in colorectal cancer from African Americans. Clin Cancer Res.2003.9(3):1112-7.
[100]Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet.2000. 355(9217):1745-50.
[101]Ries LA, Wingo PA, Miller DS, et al. The annual report to the nation on the status of cancer,1973-1997, with a special section on colorectal cancer. Cancer.2000.88(10):2398-424.
[102]Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women:principal results From the Women's Health Initiative randomized controlled trial. JAMA.2002.288(3):321-33.
[103]Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med.2004.350(10):991-1004.
[104]Newcomb PA, Storer BE. Postmenopausal hormone use and risk of large-bowel cancer. J Natl Cancer Inst.1995.87(14):1067-71.
[105]Mandelson MT, Miglioretti D, Newcomb PA, Harrison R, Potter JD. Hormone replacement therapy in relation to survival in women diagnosed with colon cancer. Cancer Causes Control.2003.14(10):979-84.
[106]Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives:cohort data from the Royal College of General Practitioner's oral contraception study. BMJ.2007.335(7621):651.
[107]Fernandez E, La Vecchia C, Balducci A, Chatenoud L, Franceschi S, Negri E. Oral contraceptives and colorectal cancer risk:a meta-analysis. Br J Cancer.2001.84(5):722-7.
[108]Franceschi S, Gallus S, Talamini R, Tavani A, Negri E, La Vecchia C. Menopause and colorectal cancer. Br J Cancer.2000.82(11):1860-2.
[109]Zhang W, Press OA, Haiman CA, et al. Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. J Clin Oncol.2007.25(24):3726-31.
[110]Press OA, Zhang W, Gordon MA, et al. Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer. Cancer Res.2008.68(8):3037-42.
[111]Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol.2002.20(6):1491-8.
[112]Woods SE, Basho S, Engel A. The influence of gender on colorectal cancer stage:the state of Ohio,1996-2001. J Womens Health (Larchmt).2006.15(7):877-81.
[113]McArdle CS, McMillan DC, Hole DJ. Male gender adversely affects survival following surgery for colorectal cancer. Br J Surg.2003.90(6):711-5.
[114]Wichmann MW, Muller C, Hornung HM, Lau-Werner U, Schildberg FW. Gender differences in long-term survival of patients with colorectal cancer. Br J Surg.2001.88(8): 1092-8.
[115]Koo JH, Jalaludin B, Wong SK, Kneebone A, Connor SJ, Leong RW. Improved survival in young women with colorectal cancer. Am J Gastroenterol.2008.103(6):1488-95.
[116]Angell-Andersen E, Tretli S, Coleman MP, Langmark F, Grotmol T. Colorectal cancer survival trends in Norway 1958-1997. Eur J Cancer.2004.40(5):734-42.
[117]Sica V, Nola E, Contieri E, et al. Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res.1984.44(10):4670-4.
[118]Enmark E, Pelto-Huikko M, Grandien K, et al. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997.82(12):4258-65.
[119]Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW. Selective loss of estrogen receptor beta in malignant human colon. Cancer Res.2000.60(2):245-8.
[120]Qiu Y, Waters CE, Lewis AE, Langman MJ, Eggo MC. Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta. J Endocrinol.2002.174(3):369-77.
[121]Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer.2003.39(9):1251-8.
[122]Martineti V, Picariello L, Tognarini I, et al. ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr Relat Cancer.2005.12(2):455-69.
[123]Xie LQ, Yu JP, Luo HS. Expression of estrogen receptor beta in human colorectal cancer. World J Gastroenterol.2004.10(2):214-7.
[124]Hsu HH, Cheng SF, Wu CC, et al. Apoptotic effects of over-expressed estrogen receptor-beta on LoVo colon cancer cell is mediated by p53 signalings in a ligand-dependent manner. Chin J Physiol.2006.49(2):110-6.
[125]Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics.2006.7(8):497-508.
[126]Galluzzo P, Caiazza F, Moreno S, Marino M. Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr Relat Cancer.2007.14(1): 153-67.
[127]Doolan CM, Harvey BJ. A Galphas protein-coupled membrane receptor, distinct from the classical oestrogen receptor, transduces rapid effects of oestradiol on [Ca2+]i in female rat distal colon. Mol Cell Endocrinol.2003.199(1-2):87-103.
[128]Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol.2006.20(9):1996-2009.
[129]Marino M, Galluzzo P, Leone S, Acconcia F, Ascenzi P. Nitric oxide impairs the 17beta-estradiol-induced apoptosis in human colon adenocarcinoma cells. Endocr Relat Cancer.2006.13(2):559-69.
[130]Gilad LA, Schwartz B. Association of estrogen receptor beta with plasma-membrane caveola components:implication in control of vitamin D receptor. J Mol Endocrinol.2007. 38(6):603-18.
[131]Caiazza F, Galluzzo P, Lorenzetti S, Marino M.17Beta-estradiol induces ERbeta up-regulation via p38/MAPK activation in colon cancer cells. Biochem Biophys Res Commun. 2007.359(1):102-7.