Cancer Risk and Environmental Exposures

癌症风险和环境暴露

基本信息

批准号：
7593167
负责人：
KENNETH CANTOR
金额：
$ 0.13万
依托单位：
DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7593167
关键词：
Argentina Arsenic Bladder Body Burden Brain Cancer Patient Case-Control Studies Characteristics Chemicals Chile China Chlorinated Hydrocarbons Class Coal Cohort Studies Colon, Rectum Consumption Data Data Analyses Databases Disinfection Environment Environmental Exposure Environmental Risk Factor Epidemiology Esophagus Exposure to Female Finland General Population Genes Genetic Genetic Polymorphism Glass Goals Hobbies Home environment Iowa K-ras Gene Kidney Licensing Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of lung Measurement Measures Methods Minnesota Missouri Monitor Mutation New England Non-Hodgkin&apos s Lymphoma Non-Malignant OGG1 gene Occupational Oxidative Stress Pancreas Pathogenesis Pathology Pattern Play Polychlorinated Biphenyls Population Purpose Radio Radon Rectal Cancer Research Risk Risk Estimate Risk Factors Role Serum Single Nucleotide Polymorphism Smoke Sputum Standards of Weights and Measures Stomach TP53 gene Taiwan Techniques Time Update Water Water Supply Woman Work Workplace cancer risk detector dosimetry drinking water improved men mortality novel novel strategies sex

项目摘要

Risk factors for cancer from the ambient environment are studied to identify specific chemicals and classes of contaminants, to investigate mechanisms of action, and to estimate the contribution of environmental factors to cancer in the general population. Case-control studies are conducted on non-Hodgkin's lymphoma and cancers of the lung, bladder, colon, rectum, stomach, esophagus, brain, pancreas, and kidney. Exposures include drinking water contaminants, especially disinfection byproducts and arsenic; airborne radon in homes; and body burdens of chlorinated hydrocarbons from past environmental or dietary exposures. Related case-control studies in Iowa showed excess risks for rectal cancer in both sexes and bladder and brain cancers among men after long-term consumption of disinfection byproducts in drinking water. Analysis of these data with an improved and updated assessment of exposure to disinfection byproducts is underway. The risk of brain cancer after such exposures is being further investigated in the upper midwest as is lung cancer risk in Iowa. We earlier found an association between PCBs in stored serum and subsequent risk of non-Hodgkin's lymphoma. Recent work showed that the higher-chlorinated congeners as well as certain immunotoxic congener groups were most strongly associated with risk of NHL. Further analyses showed no association with several other organochlorines. Studies by others in Taiwan, Chile, and Argentina have described a high risk for bladder and other cancers after exposure to arsenic in drinking water supplies at levels several times the maximum contaminant limit. A case-control study in northern New England is evaluating bladder risk at lower levels of arsenic that are more common in the U.S. A case-control study of lung cancer and residential radon among Missouri women is unique because it used a novel radon detector which integrates residential radon exposure over the past 30 years (CR-39 detector). A significant excess lung cancer risk was observed with increasing radon concentrations when measure by the CR-39 detector but not when measured by standard radon dosimetry. We are further validating the Iowa and Missouri glass dosimetry technique by exposing the dosimeters to glass objects in homes in Minnesota and Finland that have had radon measurements made every year for the past 15 years. Pathology and epidemiology data from the Iowa and Missouri radon studies will be combined for a pooled analysis. Analysis of the interaction of radon with genetic polymorphisms is anticipated. K-Ras mutations were elevated among female lung cancer patients exposed to unvented coal smoke in China. Among healthy women exposed to smoky coal emissions, mutations in the p53 gene, and to a lesser extent, the K-ras gene, were elevated in non-malignant epithelial cells taken from the sputum. Further results suggested that single nucleotide polymorphisms in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population. A retrospective cohort study of licensed radio amateurs, including an occupational component, is evaluating patterns of mortality that may be related to hobby or workplace exposures. Several activities are developing new approaches, and improving existing methods, of exposure assessment in studies of general environmental exposures. These are required to better estimate risk and to detect the relatively small increases in risk often encountered in such studies. Databases of water contaminants, gathered for routine monitoring purposes, are being used to estimate past exposures to subjects in case-control studies.

研究了环境环境中癌症的危险因素，以鉴定特定的化学物质和污染物类别，以研究作用机制，并估算环境因素对普通人群的贡献。病例对照研究是对肺，膀胱，结肠，直肠，胃，食道，脑，胰腺和肾脏的肺淋巴瘤和癌症进行的。暴露包括饮用水污染物，尤其是消毒副产品和砷；空降ra在房屋中；以及过去的环境或饮食暴露中的氯化碳氢化合物负担。在爱荷华州进行的相关病例对照研究表明，在长期消费饮用水中消毒副产品后，男性，膀胱和脑癌的直肠癌的风险过多。对这些数据进行分析，并进行了改进和更新的消毒副产品的暴露评估。在爱荷华州的肺癌风险和肺癌风险中，正在进一步研究这种暴露后脑癌的风险。我们早些时候发现PCB在储存的血清中与随后的非霍奇金淋巴瘤风险之间的关联。最近的工作表明，高氯的同类物以及某些免疫毒性的同类物组与NHL风险最密切相关。进一步的分析显示，与其他几种有机氯无关。台湾，智利和阿根廷其他人的研究描述了膀胱和其他癌症在饮用水供应中接触砷后的高风险，其水平是最大污染物极限的几倍。在新英格兰北部进行的一项病例对照研究正在评估砷含量较低的膀胱风险，这在美国更为常见，这在密苏里州妇女中对肺癌和住宅radon的病例对照研究是独一无二的，因为它使用了一种新型的ra探测器，它使用了一种在过去30年中整合住宅ra的新型探测器（CR-39探测器）（CR-39探测者）。当CR-39检测器测量ra浓度时，观察到显着的过量肺癌风险，而通过标准ra剂量测定测量时，则观察到肺癌的风险。我们正在进一步验证爱荷华州和密苏里州玻璃剂量测定技术，通过将剂量计暴露于明尼苏达州和芬兰的房屋中的玻璃物体中，这些剂量在过去15年中每年进行了ra尺测量。来自爱荷华州和密苏里州ra研究的病理和流行病学数据将合并以进行汇总分析。预计将分析ra与遗传多态性的相互作用。在中国暴露于未发泄煤烟的女性肺癌患者中，K-RAS突变升高。在暴露于烟熏煤发射的健康女性中，p53基因的突变和较小程度的K-Ras基因在从痰液中取的非恶性上皮细胞中升高。进一步的结果表明，氧化应激相关基因AKR1C3和OGG1中的单核苷酸多态性可能在该人群的肺癌发病机理中起作用。一项对包括职业成分在内的许可无线电业余爱好者的回顾性队列研究是评估可能与业余爱好或工作场所暴露有关的死亡模式。在一般环境暴露的研究中，几项活动正在开发新方法，并改善现有方法。这些研究需要更好地估计风险，并检测此类研究经常遇到的相对较小的风险增加。用于常规监测目的的水污染物的数据库正在用于估计案例对照研究中对受试者的过去暴露。