铜铁矿工人肺癌巢式病例对照研究
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摘要
肺癌是目前全世界范围内发病率和死亡率最高的恶性肿瘤,其上升速度也最快。尤其在近些年,女性肺癌发病率有上升的趋势。近20多年来,我国的肺癌发病率以每年11%的速度递增,发病率已由原来肿瘤发病的第6位上升到第2位,而死亡率已经由20世纪70年代第4位上升到首位,总患病率已占到男性恶性肿瘤的首位。我国目前每年新发肺癌人数已达21万人之多,其中非小细胞肺癌占70%-80%。随着城市化,工业化的推进,肺癌的致病因素日趋多样化和严重化,在世界范围内肺癌已经成为影响人们健康的重要问题。
在生产上或职业中长期接触职业性致癌物引发的肺癌,称为职业性肺癌。近些年陆续有报道金属矿山工人肺癌高发[39,40]。为探讨铜铁矿作业工人肺癌的发病危险因素及其交互作用,分析铜铁矿职业性有害因素的变化规律及评价粉尘防制措施的效果,本研究在队列前期研究的基础上,选择湖北两家铜铁矿1970年1月1日至1972年12月31日之间登记在册且工作一年以上的所有职工建立队列,共计11016人,随访至2003年12月31日。研究内容包括三大部分:1、铜铁矿作业场所职业性有害因素的测定和分析;2、铜铁矿作业工人肺癌巢式病例对照研究;3、铜铁矿肺癌主要危险因素的交互作用分析。
第一部分铜铁矿作业场所职业有害因素的测定与分析
本部分通过收集湖北两家个某铜铁矿作业场所历史监测资料和开展铜铁矿作业现场职业性有害因素的监测工作,全面掌握铜铁矿作业场所职业危害的特点和严重程度,为铜铁矿及同类企业开展降尘措施和工人健康监护提供科学依据。
收集并整理湖北2个铜铁矿1952～2004年的粉尘监测资料,1952年以后部分缺乏记录和1952年以前的监测资料,由测尘员、工业卫生人员、经验丰富的工人以及安全技术工程人员根据当时的工作条件,并结合我国的降尘防尘措施、生产工艺改革等情况进行估算。监测内容主要包括空气中总粉尘、呼吸性粉尘、粉尘游离二氧化硅含量、粉尘分散度、空气和积尘30种化学元素含量、放射性氡子体、γ射线以及17种多环芳烃等。
湖北铜铁矿历史监测资料以及定期的作业环境监测数据显示,铜铁矿作业场所总粉尘浓度在20世纪50年代初最高,平均大约在11.00 mg/m~3左右,个别工种可达20.83 mg/m~3, 50年代开始粉尘浓度总体呈下降趋势,60年代为5～7.0mg/m~3,70年代2.5~7.5 mg/m~3,80年代为1.7~2.7 mg/m~3,90年代至随访结束为1.5～2.5 mg/m~3。铜铁矿作业场所粉尘的分散度非常高,空气动力学直径小于5μm的颗粒在铁矿一些作业点可达70.33%,在铜矿一些作业点甚至达到90.63%。铜矿积尘的游离二氧化硅含量平均为10.6%。作业岗位暴露粉尘浓度较高的工种有风钻工、爆破工,采掘工和爆破工等。铜铁矿作业场所空气中和积尘中化学元素分析结果提示砷、镉等可能致癌元素均未检出,积尘中铝含量较高,平均水平在铜矿和铁矿分别为5033.3μg/g和11166.7μg/g。此外,铜铁矿钴、锰、钼和钛含量均检出较高,铜铁矿积尘中铁元素在铜矿和铁矿分别高达137666.7μg/g和143333.3μg/g。1988年的监测显示检出多环芳烃总浓度为22.58μg/m~3,其中大部分多环芳烃均为致癌性不明或无致癌性。在1988年的监测数据显示铜矿作业场所氡子体0.07WL,铁矿为0.01WL;γ射线铜矿平均为0.64 mR/hr,铁矿为0.025 mR/hr。2007年又对铜铁矿氡子体及γ射线进行了监测,铜矿氡子体为0.038WL,γ射线铜矿为0.022 mR/hr,铁矿为0.075 mR/hr。
第二部分铜铁矿工人肺癌巢式病例对照研究
本部分以湖北两家铜铁矿队列人群的确诊肺癌为病例进行巢式病例对照研究,以初步明确铜铁矿肺癌高发的主要危险因素以及肺癌发病危险度与这些危险因素之间的关联强度,并提出改进和预防措施。
选择湖北两家铜铁矿1970年1月1日至1972年12月31日之间登记在册且工作一年以上的所有职工建立队列,追访肺癌死亡从1972年1月1日开始到2003年12月31日为止,选择在此期间所有死于肺癌的队列成员作为病例。共收集病例215例(男215例,女12例排除)。对于每一病例,以同性别,同厂矿,同出生年代作为匹配原则选择4例对照进行1:4匹配。若对照年龄小于所匹配病例的患病年龄则予以排除,共选择对照860例。
本研究发现,调整吸烟因素后接尘组患肺癌的危险性明显高于非接尘(OR=1.78,95%CI:1.29~2.45)。在铜铁矿,随着累积接尘量升高,肺癌危险度也随之上升,在低、中和高接尘组OR值分别为1.36、1.74和2.31,呈明显的剂量反应关系。随着矽肺期别的上升,肺癌的危险度也增加。经吸烟调整后,Ⅰ期、Ⅱ期和Ⅲ期矽肺组OR值分别为2.66、3.18和2.92。由于矽肺与高累积量的粉尘接触相关,本研究不能排除矽肺中肺癌增高是长期粉尘接触引起。本研究发现吸烟者在病例所占比例(87%)明显高于对照组(68%),经接尘调整后,吸烟低、中、高组OR值均显著高于对照组,OR值分别为2.40、4.16和2.67。本研究还发现有肺结核病史的矿工患肺癌的危险度是无肺结核病史的矿工患肺癌的危险度的3.42倍。本研究将是否吸烟、是否接尘、矽肺和结核等因素纳入非条件logistic回归模型,并用逐步回归法筛选变量,有统计学意义的肺癌危险因素是吸烟、肺结核病史和接尘。根据OR值的大小,吸烟(OR=3.7)是肺癌最主要的危险因素,其次是肺结核病史(OR=3.42),最后是接尘(OR=1.66)。
第三部分铜铁矿肺癌主要危险因素的交互作用分析
本部分对第二部分logistic回归模型筛选出铜铁矿矿工肺癌的主要危险因素:吸烟、接尘和结核,利用logistic回归模型纳入研究因素交互项得出RR值,并用Rothman和Hosmer指标进行交互作用评价。
本部分研究的肺癌与病例同第二部分。研究发现接尘与吸烟对肺癌的交互效应超额相对危险度RERI为1.93,归因交互效应百分比AP为33%。交互效应指数S为1.67,但其可信区间无统计学意义,所以本研究认为吸烟与接尘对肺癌死亡无相加交互作用。结核病史与吸烟对肺癌的交互效应超额相对危险度RERI为9.13,归因交互效应百分比AP为59%。吸烟与结核病史的交互效应指数S达到2.74,但是其可信区间同样无统计学意义,所以本研究认为吸烟与结核病史对肺癌死亡无相加交互作用。
结论
本研究建立铜铁矿作业工人的研究队列,结合铜铁矿职业性有害因素的测定和分析,通过对铜铁矿进行巢式病例对照研究探讨铜铁矿作业工人肺癌的发病危险因素,并采用Rothman和Hosmer用于评价交互作用的指标进行交互作用评价,得出以下主要结论:
1、铜铁矿作业场所粉尘浓度在上世纪50年代初高达11.00 mg/m~3,之后粉尘浓度呈现下降趋势,尤其是50年代末下降明显,60年代为5～7.0mg/m~3,70年代2.5~7.5 mg/m~3,80年代为1.7~2.7 mg/m~3,90年代至随访结束为1.5～2.5 mg/m~3。肯定了我国防尘八字方针的大力推行和生产工艺改进等防尘降尘措施的开展效果;研究提示铜铁矿作业场所其它职业性有害因素比较复杂,生产性粉尘中含铅、铜、铁等元素,铜矿作业点总多环芳烃浓度达到22.58μg/m~3,氡子体达到0.07WL,应加大作业岗位职业有害因素的控制力度。
2、吸烟(OR=3.7)是铜铁矿肺癌的最主要危险因素,其次是肺结核病史(OR=3.42),最后是接尘(OR=1.66)。铜铁矿肺癌发病的重要危险因素:吸烟、接尘与肺癌呈剂量反应关系,本研究不能确认患矽肺是肺癌的危险因素。
3、本研究认为在铜铁矿矿工中,吸烟和接尘对矿工肺癌的发病无交互作用,结核病史与吸烟对矿工肺癌发病同样没有交互作用。
Lung cancer is the highest mortality and morbidity of malignant tumor in the world. Especially in recent years, women lung cancer has been increased gradually. In past 20 years, the incidence of lung cancer increased by 10% annually in China. Since the beginning of 21st century, lung cancer has been the first cause of death in China, the mortality of lung cancer rose from the top four in 1970s to the first. The number of new lung cancer has reached as many as 210,000 people in China each year, including non-small cell carcinoma accounts for 70-80%. It can be predicted that the influencing factors of lung cancer are becoming more diverse and serious. With acceleration of industrialization and urbanization, lung cancer has become a serious public health problem all over the world.
The aim of this study was to investigate the risk factors of lung cancer and analyze interaction among them. and to evaluate the effect of dust control techniques on the mortality of lung cancer. On the basis of previous cohort study, the 11016 copper and iron miners employed during 1960 to 1974 and at least 1 year from Hubei province, were extended followed up to the end of 2004. The study included 3 sections: section1, Evaluation of occupational hazards at the workplace of copper and iron mines; section 2, A nested case-control study of lung cancer in copper and iron miners ; section 3, A study of interactive analysis on lung cancer risk factors.
SectionⅠ
Evaluation of occupational hazards in the workplace of copper mine and iron mine
The objective of this section was to evaluate the occupational hazards at the workplace in copper and iron mines by collecting historical data and records of occupational hazards. and to provide useful information for the health surveillance as well as protective policy-making in these mines and other related corporations.
The monitoring of occupational hazards in Hubei copper and iron mines was initiated in 1950s. The historical data of dust monitoring during 1952～2004 was abstracted from the records of copper and iron mines determined by local industrial hygienists. For no record of dust exposure before 1952, the dust concentrations were estimated by specialists, industrial hygienists and experienced workers, mainly according to the current conditions of the workplace and dust control. Occupational hazards including total dust, respiratory dust, 30 chemistry elements, radon,γ-radiation and 17 polycyclic aromatic hydrocarbons (PAHs) were determined by specialists in Tongji Medical College in 1989 and 2007. The results were used to compare with monitor data by local industrial hygienists.
The results showed that the total dust concentrations were very high in 1950s, with an average concentration of 11.00 mg/m3. However, the concentrations decreased sharply at the end of 1950s because wet suppression and other dust control techniques were installed and used. The concentration of dust ranged from 5.0 to 7.0mg/m3 during 1960s, it ranged from 2.5 to 7.5mg/m3 during 1970s and 1.7 to 2.7mg/m3 during 1980s, dust concentration changed from 1.5 to 2.5mg/m3 between 1990s and the end of follow-up. For the decentralization degree of copper and iron mine dust, the particles with aerodynamic diameter less than 5μm accounted for about 80.48%. The free silica content was about 27.5% in total dust and 9.7% in respiratory dust. The total dust concentrations of job titles under ground were higher than that on the ground. And the dust concentrations of blasting, drilling, crushing and packing were relatively high. The result of elements amount of dust samples were that the aluminum content in air and bulk dust was as high as 5033.3μg/g in copper mine and 11166.7μg/g in iron mine. The iron content in dust reached to 137666.7μg/g in copper mine and 11166.7μg/g in iron mine.The whole PAHs concentration was as high as 22.58μg/m3. Most of them in copper and iron mine were no carcinogenic PAHs. Radon andγ-radiation are not very high in copper and iron mines.
SectionⅡ
A nested case-control study of lung cancer in copper mine and iron miner
The aim of this section was to explore the relationship between metal mine dust and primary lung cancer, and to evaluate the effects of smoking and other potential occupational factors on risk of lung cancer by a nested case-control study.
A nested case-control study of 215 male lung cancer cases and 860 controls was initiated from a cohort study of 11016 subjects employed at least 1 year between 1972 and 1974 in copper and iron mines. One lung cancer case was matched to about 4 controls, based on age (decade of birth), sex, and mine. Controls that died at an age younger than the age at diagnosis of lung cancer of corresponding cases were excluded from analysis.
The results indicated that the cumulative dust exposure, smoking, silicosis and history of TB were the possible risk factors of lung cancer, after adjusting for smoking. Comparing to dust-free group, the relative risk of lung cancer increased when cumulative exposures to total dust become higher. The positive dose-response relationship was observed between cumulative dust exposure and lung cancer. Smoking was significantly associated with risk of lung cancer; the relative risk of medial smoking group(OR=4.16) and low smoking group(OR=2.40) were higher than the non-smoking group. The risk suffering from lung caner of workers with silicosis was 1.42 times high as comparison with non-silicosis. The results could confirm the effect of silicosis on lung cancer because silicosis means high cumulative dust exposure. The later also caused high risk of lung cancer. And, comparing to worker without TB, the relative risk of history of TB was 3.42 (95%CI:1.54~7.87). The multivariate unconditional Logistic regression was performed to screen the risk factors of lung cancer. The main risk factors for lung cancer were smoking, dust exposure and history of TB.
SectionⅢ
A study of interaction among lung cancer risk factors
The result from part II showed that the high risk factors of lung cancer in copper and iron mines were cigarette smoking,dust exposure and history of TB. Their ORs were 3.7, 1.66 and 3.42. Here, we calculated RRs through putting interaction term into logistic regression model, to evaluate the interaction on lung cancer risk factors by the three measures of biological interaction(RERI, AP and S) presented by Rothman.
The lung cancer and matched controls in part II were used in the analysis. This study indicated that dust exposure had not an additive model synergism on cigarette smoking. The relative excess risk due to interactions (RERI) was 1.93. the attributable proportion due to interaction (AP) was 33 % and the synergy index(S) was 1.67. History of TB also had not an additive model synergism on cigarette smoking. The relative excess risk due to interactions (RERI) was 9.13, the attributable proportion due to interaction (AP) was 59% and the synergy index (S) was 2.74.
Conclusion
In this study, the possible occupational hazards in workplaces of two iron and copper mines were analyzed according to the results of long term monitoring. And a nested case-control study was conducted to evaluate potential risk factors of lung cancer in copper and iron mines. The three measures of biological interaction (RERI, AP and S) presented by Rothman were evaluated the interaction on lung cancer risk factors. The conclusions and findings were as follows:
1. The average total dust concentration at the workplaces of copper and iron mines was as high as 11.00 mg/m~3 at the beginning of 1950s. The concentration ranged from 5.0 to 7.0mg/m~3 during 1960s, it ranged from 2.5 to 7.5mg/m~3 during 1970s and 1.7 to 2.7mg/m~3 during 1980s, dust concentration changed from 1.5 to 2.5mg/m~3 between 1990s and the end of follow-up. It shows that the total dust concentrations began decreasing, especially at the end of 1950s. which was attributed to wet suppression and other dust control techniques were installed and used. At the same time, other occupational hazards in copper and iron mines are complex. Among them, the concentrations of PAHs and radon were up to 22.58μg/m~3 and 0.07WL respectively at many worksites.
2. The results showed that smoking , dust exposure and history of TB were main risk factors of lung cancer in copper and iron miners. The positive pose-response trend was shown between cumulative dust exposure and risk for lung cancer. And this study can not support that silicosis was risk factor of lung cancer.
3. Dust exposure had not an additive model synergism on cigarette smoking. and History of TB also had not an additive model synergism on cigarette smoking.
在生产上或职业中长期接触职业性致癌物引发的肺癌,称为职业性肺癌。近些年陆续有报道金属矿山工人肺癌高发[39,40]。为探讨铜铁矿作业工人肺癌的发病危险因素及其交互作用,分析铜铁矿职业性有害因素的变化规律及评价粉尘防制措施的效果,本研究在队列前期研究的基础上,选择湖北两家铜铁矿1970年1月1日至1972年12月31日之间登记在册且工作一年以上的所有职工建立队列,共计11016人,随访至2003年12月31日。研究内容包括三大部分:1、铜铁矿作业场所职业性有害因素的测定和分析;2、铜铁矿作业工人肺癌巢式病例对照研究;3、铜铁矿肺癌主要危险因素的交互作用分析。
第一部分铜铁矿作业场所职业有害因素的测定与分析
本部分通过收集湖北两家个某铜铁矿作业场所历史监测资料和开展铜铁矿作业现场职业性有害因素的监测工作,全面掌握铜铁矿作业场所职业危害的特点和严重程度,为铜铁矿及同类企业开展降尘措施和工人健康监护提供科学依据。
收集并整理湖北2个铜铁矿1952～2004年的粉尘监测资料,1952年以后部分缺乏记录和1952年以前的监测资料,由测尘员、工业卫生人员、经验丰富的工人以及安全技术工程人员根据当时的工作条件,并结合我国的降尘防尘措施、生产工艺改革等情况进行估算。监测内容主要包括空气中总粉尘、呼吸性粉尘、粉尘游离二氧化硅含量、粉尘分散度、空气和积尘30种化学元素含量、放射性氡子体、γ射线以及17种多环芳烃等。
湖北铜铁矿历史监测资料以及定期的作业环境监测数据显示,铜铁矿作业场所总粉尘浓度在20世纪50年代初最高,平均大约在11.00 mg/m~3左右,个别工种可达20.83 mg/m~3, 50年代开始粉尘浓度总体呈下降趋势,60年代为5～7.0mg/m~3,70年代2.5~7.5 mg/m~3,80年代为1.7~2.7 mg/m~3,90年代至随访结束为1.5～2.5 mg/m~3。铜铁矿作业场所粉尘的分散度非常高,空气动力学直径小于5μm的颗粒在铁矿一些作业点可达70.33%,在铜矿一些作业点甚至达到90.63%。铜矿积尘的游离二氧化硅含量平均为10.6%。作业岗位暴露粉尘浓度较高的工种有风钻工、爆破工,采掘工和爆破工等。铜铁矿作业场所空气中和积尘中化学元素分析结果提示砷、镉等可能致癌元素均未检出,积尘中铝含量较高,平均水平在铜矿和铁矿分别为5033.3μg/g和11166.7μg/g。此外,铜铁矿钴、锰、钼和钛含量均检出较高,铜铁矿积尘中铁元素在铜矿和铁矿分别高达137666.7μg/g和143333.3μg/g。1988年的监测显示检出多环芳烃总浓度为22.58μg/m~3,其中大部分多环芳烃均为致癌性不明或无致癌性。在1988年的监测数据显示铜矿作业场所氡子体0.07WL,铁矿为0.01WL;γ射线铜矿平均为0.64 mR/hr,铁矿为0.025 mR/hr。2007年又对铜铁矿氡子体及γ射线进行了监测,铜矿氡子体为0.038WL,γ射线铜矿为0.022 mR/hr,铁矿为0.075 mR/hr。
第二部分铜铁矿工人肺癌巢式病例对照研究
本部分以湖北两家铜铁矿队列人群的确诊肺癌为病例进行巢式病例对照研究,以初步明确铜铁矿肺癌高发的主要危险因素以及肺癌发病危险度与这些危险因素之间的关联强度,并提出改进和预防措施。
选择湖北两家铜铁矿1970年1月1日至1972年12月31日之间登记在册且工作一年以上的所有职工建立队列,追访肺癌死亡从1972年1月1日开始到2003年12月31日为止,选择在此期间所有死于肺癌的队列成员作为病例。共收集病例215例(男215例,女12例排除)。对于每一病例,以同性别,同厂矿,同出生年代作为匹配原则选择4例对照进行1:4匹配。若对照年龄小于所匹配病例的患病年龄则予以排除,共选择对照860例。
本研究发现,调整吸烟因素后接尘组患肺癌的危险性明显高于非接尘(OR=1.78,95%CI:1.29~2.45)。在铜铁矿,随着累积接尘量升高,肺癌危险度也随之上升,在低、中和高接尘组OR值分别为1.36、1.74和2.31,呈明显的剂量反应关系。随着矽肺期别的上升,肺癌的危险度也增加。经吸烟调整后,Ⅰ期、Ⅱ期和Ⅲ期矽肺组OR值分别为2.66、3.18和2.92。由于矽肺与高累积量的粉尘接触相关,本研究不能排除矽肺中肺癌增高是长期粉尘接触引起。本研究发现吸烟者在病例所占比例(87%)明显高于对照组(68%),经接尘调整后,吸烟低、中、高组OR值均显著高于对照组,OR值分别为2.40、4.16和2.67。本研究还发现有肺结核病史的矿工患肺癌的危险度是无肺结核病史的矿工患肺癌的危险度的3.42倍。本研究将是否吸烟、是否接尘、矽肺和结核等因素纳入非条件logistic回归模型,并用逐步回归法筛选变量,有统计学意义的肺癌危险因素是吸烟、肺结核病史和接尘。根据OR值的大小,吸烟(OR=3.7)是肺癌最主要的危险因素,其次是肺结核病史(OR=3.42),最后是接尘(OR=1.66)。
第三部分铜铁矿肺癌主要危险因素的交互作用分析
本部分对第二部分logistic回归模型筛选出铜铁矿矿工肺癌的主要危险因素:吸烟、接尘和结核,利用logistic回归模型纳入研究因素交互项得出RR值,并用Rothman和Hosmer指标进行交互作用评价。
本部分研究的肺癌与病例同第二部分。研究发现接尘与吸烟对肺癌的交互效应超额相对危险度RERI为1.93,归因交互效应百分比AP为33%。交互效应指数S为1.67,但其可信区间无统计学意义,所以本研究认为吸烟与接尘对肺癌死亡无相加交互作用。结核病史与吸烟对肺癌的交互效应超额相对危险度RERI为9.13,归因交互效应百分比AP为59%。吸烟与结核病史的交互效应指数S达到2.74,但是其可信区间同样无统计学意义,所以本研究认为吸烟与结核病史对肺癌死亡无相加交互作用。
结论
本研究建立铜铁矿作业工人的研究队列,结合铜铁矿职业性有害因素的测定和分析,通过对铜铁矿进行巢式病例对照研究探讨铜铁矿作业工人肺癌的发病危险因素,并采用Rothman和Hosmer用于评价交互作用的指标进行交互作用评价,得出以下主要结论:
1、铜铁矿作业场所粉尘浓度在上世纪50年代初高达11.00 mg/m~3,之后粉尘浓度呈现下降趋势,尤其是50年代末下降明显,60年代为5～7.0mg/m~3,70年代2.5~7.5 mg/m~3,80年代为1.7~2.7 mg/m~3,90年代至随访结束为1.5～2.5 mg/m~3。肯定了我国防尘八字方针的大力推行和生产工艺改进等防尘降尘措施的开展效果;研究提示铜铁矿作业场所其它职业性有害因素比较复杂,生产性粉尘中含铅、铜、铁等元素,铜矿作业点总多环芳烃浓度达到22.58μg/m~3,氡子体达到0.07WL,应加大作业岗位职业有害因素的控制力度。
2、吸烟(OR=3.7)是铜铁矿肺癌的最主要危险因素,其次是肺结核病史(OR=3.42),最后是接尘(OR=1.66)。铜铁矿肺癌发病的重要危险因素:吸烟、接尘与肺癌呈剂量反应关系,本研究不能确认患矽肺是肺癌的危险因素。
3、本研究认为在铜铁矿矿工中,吸烟和接尘对矿工肺癌的发病无交互作用,结核病史与吸烟对矿工肺癌发病同样没有交互作用。
Lung cancer is the highest mortality and morbidity of malignant tumor in the world. Especially in recent years, women lung cancer has been increased gradually. In past 20 years, the incidence of lung cancer increased by 10% annually in China. Since the beginning of 21st century, lung cancer has been the first cause of death in China, the mortality of lung cancer rose from the top four in 1970s to the first. The number of new lung cancer has reached as many as 210,000 people in China each year, including non-small cell carcinoma accounts for 70-80%. It can be predicted that the influencing factors of lung cancer are becoming more diverse and serious. With acceleration of industrialization and urbanization, lung cancer has become a serious public health problem all over the world.
The aim of this study was to investigate the risk factors of lung cancer and analyze interaction among them. and to evaluate the effect of dust control techniques on the mortality of lung cancer. On the basis of previous cohort study, the 11016 copper and iron miners employed during 1960 to 1974 and at least 1 year from Hubei province, were extended followed up to the end of 2004. The study included 3 sections: section1, Evaluation of occupational hazards at the workplace of copper and iron mines; section 2, A nested case-control study of lung cancer in copper and iron miners ; section 3, A study of interactive analysis on lung cancer risk factors.
SectionⅠ
Evaluation of occupational hazards in the workplace of copper mine and iron mine
The objective of this section was to evaluate the occupational hazards at the workplace in copper and iron mines by collecting historical data and records of occupational hazards. and to provide useful information for the health surveillance as well as protective policy-making in these mines and other related corporations.
The monitoring of occupational hazards in Hubei copper and iron mines was initiated in 1950s. The historical data of dust monitoring during 1952～2004 was abstracted from the records of copper and iron mines determined by local industrial hygienists. For no record of dust exposure before 1952, the dust concentrations were estimated by specialists, industrial hygienists and experienced workers, mainly according to the current conditions of the workplace and dust control. Occupational hazards including total dust, respiratory dust, 30 chemistry elements, radon,γ-radiation and 17 polycyclic aromatic hydrocarbons (PAHs) were determined by specialists in Tongji Medical College in 1989 and 2007. The results were used to compare with monitor data by local industrial hygienists.
The results showed that the total dust concentrations were very high in 1950s, with an average concentration of 11.00 mg/m3. However, the concentrations decreased sharply at the end of 1950s because wet suppression and other dust control techniques were installed and used. The concentration of dust ranged from 5.0 to 7.0mg/m3 during 1960s, it ranged from 2.5 to 7.5mg/m3 during 1970s and 1.7 to 2.7mg/m3 during 1980s, dust concentration changed from 1.5 to 2.5mg/m3 between 1990s and the end of follow-up. For the decentralization degree of copper and iron mine dust, the particles with aerodynamic diameter less than 5μm accounted for about 80.48%. The free silica content was about 27.5% in total dust and 9.7% in respiratory dust. The total dust concentrations of job titles under ground were higher than that on the ground. And the dust concentrations of blasting, drilling, crushing and packing were relatively high. The result of elements amount of dust samples were that the aluminum content in air and bulk dust was as high as 5033.3μg/g in copper mine and 11166.7μg/g in iron mine. The iron content in dust reached to 137666.7μg/g in copper mine and 11166.7μg/g in iron mine.The whole PAHs concentration was as high as 22.58μg/m3. Most of them in copper and iron mine were no carcinogenic PAHs. Radon andγ-radiation are not very high in copper and iron mines.
SectionⅡ
A nested case-control study of lung cancer in copper mine and iron miner
The aim of this section was to explore the relationship between metal mine dust and primary lung cancer, and to evaluate the effects of smoking and other potential occupational factors on risk of lung cancer by a nested case-control study.
A nested case-control study of 215 male lung cancer cases and 860 controls was initiated from a cohort study of 11016 subjects employed at least 1 year between 1972 and 1974 in copper and iron mines. One lung cancer case was matched to about 4 controls, based on age (decade of birth), sex, and mine. Controls that died at an age younger than the age at diagnosis of lung cancer of corresponding cases were excluded from analysis.
The results indicated that the cumulative dust exposure, smoking, silicosis and history of TB were the possible risk factors of lung cancer, after adjusting for smoking. Comparing to dust-free group, the relative risk of lung cancer increased when cumulative exposures to total dust become higher. The positive dose-response relationship was observed between cumulative dust exposure and lung cancer. Smoking was significantly associated with risk of lung cancer; the relative risk of medial smoking group(OR=4.16) and low smoking group(OR=2.40) were higher than the non-smoking group. The risk suffering from lung caner of workers with silicosis was 1.42 times high as comparison with non-silicosis. The results could confirm the effect of silicosis on lung cancer because silicosis means high cumulative dust exposure. The later also caused high risk of lung cancer. And, comparing to worker without TB, the relative risk of history of TB was 3.42 (95%CI:1.54~7.87). The multivariate unconditional Logistic regression was performed to screen the risk factors of lung cancer. The main risk factors for lung cancer were smoking, dust exposure and history of TB.
SectionⅢ
A study of interaction among lung cancer risk factors
The result from part II showed that the high risk factors of lung cancer in copper and iron mines were cigarette smoking,dust exposure and history of TB. Their ORs were 3.7, 1.66 and 3.42. Here, we calculated RRs through putting interaction term into logistic regression model, to evaluate the interaction on lung cancer risk factors by the three measures of biological interaction(RERI, AP and S) presented by Rothman.
The lung cancer and matched controls in part II were used in the analysis. This study indicated that dust exposure had not an additive model synergism on cigarette smoking. The relative excess risk due to interactions (RERI) was 1.93. the attributable proportion due to interaction (AP) was 33 % and the synergy index(S) was 1.67. History of TB also had not an additive model synergism on cigarette smoking. The relative excess risk due to interactions (RERI) was 9.13, the attributable proportion due to interaction (AP) was 59% and the synergy index (S) was 2.74.
Conclusion
In this study, the possible occupational hazards in workplaces of two iron and copper mines were analyzed according to the results of long term monitoring. And a nested case-control study was conducted to evaluate potential risk factors of lung cancer in copper and iron mines. The three measures of biological interaction (RERI, AP and S) presented by Rothman were evaluated the interaction on lung cancer risk factors. The conclusions and findings were as follows:
1. The average total dust concentration at the workplaces of copper and iron mines was as high as 11.00 mg/m~3 at the beginning of 1950s. The concentration ranged from 5.0 to 7.0mg/m~3 during 1960s, it ranged from 2.5 to 7.5mg/m~3 during 1970s and 1.7 to 2.7mg/m~3 during 1980s, dust concentration changed from 1.5 to 2.5mg/m~3 between 1990s and the end of follow-up. It shows that the total dust concentrations began decreasing, especially at the end of 1950s. which was attributed to wet suppression and other dust control techniques were installed and used. At the same time, other occupational hazards in copper and iron mines are complex. Among them, the concentrations of PAHs and radon were up to 22.58μg/m~3 and 0.07WL respectively at many worksites.
2. The results showed that smoking , dust exposure and history of TB were main risk factors of lung cancer in copper and iron miners. The positive pose-response trend was shown between cumulative dust exposure and risk for lung cancer. And this study can not support that silicosis was risk factor of lung cancer.
3. Dust exposure had not an additive model synergism on cigarette smoking. and History of TB also had not an additive model synergism on cigarette smoking.
引文
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