Serum Organochlorine Levels and Primary Liver Cancer: A Nested Case-Control Study

血清有机氯水平与原发性肝癌：巢式病例对照研究

• 批准号: 7259839
• 负责人: LAWRENCE STUART ENGEL
• 金额: $ 80.1万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7259839
• 关键词: Affect; Aflatoxins; Age; Animals; Biological Markers; Birth; Blood; Blood specimen; Body Burden; California; Carcinogens; Censuses; Chemicals; Chlorinated Hydrocarbons; Clinical; Clinical Data; Collection; Consumption; Country; County; Data; Developed Countries; Developing Countries; Diagnosis; Disease Association; Epidemiologic Studies; Equipment; Exposure to; Extravasation; Farming environment; Fishes; Food Chain; Food Patterns; General Population; Health; Hepatitis B; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; In Vitro; Infection; Joints; Knowledge; Liver; Liver diseases; Liver neoplasms; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Metabolism; Nested Case-Control Study; Norway; Pesticides; Polychlorinated Biphenyls; Population; Population Study; Primary carcinoma of the liver cells; Production; Publishing; Race; Registries; Research; Research Personnel; Risk; Risk Factors; Route; Sampling; Serum; Skin Carcinoma; Time; Today; Virus; Woman; adduct; aflatoxin-albumin adduct; base; bioaccumulation; cancer diagnosis; cancer risk; case control; cohort; exposed human population; follow-up; indexing; landfill; member; men; organochlorine pesticide; programs; prospective; residence; sex

DESCRIPTION (provided by applicant): Although polychlorinated biphenyls (PCBs) and certain organochlorine pesticides induce liver tumors in animals, there is limited supporting epidemiologic data because of methodological challenges. There has also been little epidemiologic research into the risk associated with exposure to the low levels of aflatoxin, a known liver carcinogen, typically found in developed countries. We propose to investigate these relationships using already-collected serum and data from two large, population-based, prospective cohorts of men and women (total subjects =451,000) who provided blood samples and risk factor information between the mid- 1960s and mid-1970s. Follow-up and case ascertainment in these cohorts, one in Norway and one in Northern California, is very high and data on potential confounders are available. The aims of this study are to determine whether higher serum concentrations of organochlorines are related to increased risk of liver cancer; whether serum aflatoxin biomarkers are related to this risk; and if a synergy exists for these factors with each other or with HBV or HCV infection. We will include all cases of primary liver cancer diagnosed one or more years after blood draw (n=278) and a random sample of controls matched 3:1 to cases by cohort, age at blood draw, date of blood draw, sex, race, and county of residence (n =1,112 subjects total). We will measure serum concentrations of 39 PCB congeners, 11 organochlorine pesticides, and aflatoxin- albumin adducts, and assess HBV and HCV infection status using banked serum. We will also examine a second serum sample collected from a subset of subjects an average of 8 years after the primary sample. We will obtain information on potential confounders via linkage with previously collected health examination data (collected at blood draw), as well as clinical, census, and birth registry data available for each cohort. To our knowledge, this study would be the first to examine liver cancer risk in relation to body burden of PCBs. To be valid, such a study requires prospectively collected biospecimens because liver disease may affect the metabolism and subsequent elimination of organochlorines. The serum samples in this study were collected around the time that these organochlorines were banned in the U.S. and Norway and, thus, should reflect peak or near-peak levels of these chemicals in the general population of these countries. Although the production and use of these chemicals are banned in many countries, human exposure continues because of bioaccumulation in the food chain, ongoing use of organochlorine pesticides in less developed countries, leakage from equipment and landfills, and environmental persistence and redistribution. This study offers not only an efficient opportunity to examine the association of organochlorines and low-level aflatoxin exposure with risk of liver cancer, but also one of the few opportunities to study it in a methodologically rigorous way.

描述（由申请人提供）：尽管多氯联苯（PCB）和某些有机氯农药可诱导动物肝肿瘤，但由于方法学挑战，支持性流行病学数据有限。对于接触低水平黄曲霉毒素（一种已知的肝脏致癌物，通常在发达国家发现）相关的风险，也几乎没有流行病学研究。我们建议使用已经收集的血清和来自两个大型的、基于人群的、前瞻性的男性和女性队列（总受试者= 451，000）的数据来研究这些关系，这些队列提供了20世纪60年代中期和70年代中期之间的血液样本和风险因素信息。这些队列（一个在挪威，一个在北方加州）的随访和病例确定率非常高，并且可获得潜在混杂因素的数据。本研究的目的是确定较高的血清有机氯浓度是否与肝癌风险增加有关;血清黄曲霉毒素生物标志物是否与这种风险有关;以及这些因素之间是否存在协同作用，或者与HBV或HCV感染存在协同作用。我们将纳入所有在抽血后一年或一年以上诊断的原发性肝癌病例（n=278）和对照组随机样本，对照组按队列、抽血时年龄、抽血日期、性别、种族和居住县与病例3：1匹配（共n = 1，112例受试者）。我们将测量血清中39种PCB同系物、11种有机氯农药和黄曲霉毒素-白蛋白加合物的浓度，并使用库存血清评估HBV和HCV感染状况。我们还将检查在初次样本后平均8年从受试者子集中采集的第二份血清样本。我们将通过与先前收集的健康检查数据（在抽血时收集）以及每个队列的临床、人口普查和出生登记数据的关联来获得潜在混杂因素的信息。据我们所知，这项研究将是第一个研究肝癌风险与多氯联苯身体负担的关系。为了有效，这样的研究需要前瞻性地收集生物标本，因为肝脏疾病可能会影响有机氯的代谢和随后的消除。这项研究中的血清样本是在这些有机氯在美国和挪威被禁止的时候收集的，因此，应该反映这些化学品在这些国家的一般人群中的峰值或接近峰值的水平。尽管许多国家禁止生产和使用这些化学品，但由于食物链中的生物累积、欠发达国家持续使用有机氯农药、设备和垃圾填埋场的泄漏以及环境持久性和再分布，人类继续接触这些化学品。这项研究不仅提供了一个有效的机会来研究有机氯和低水平黄曲霉毒素暴露与肝癌风险的关系，而且也是以严格的方法研究它的少数机会之一。