Occupational Pesticide Use and Risk of Lymphoid Cancers

 描述（由申请人提供）：暴露于农药是广泛的，无论是在某些工作和在家庭环境中的较低水平。有一个强烈的需要量化的数据从农药的癌症风险，无论是阐明致癌的毒理学机制和支持监管。有研究表明，目前使用的某些农药可能会增加非霍奇金淋巴瘤（NHL）和其他淋巴癌（如慢性淋巴细胞白血病（CLL）和多发性骨髓瘤（MM））的风险;然而，个体研究的规模阻碍了精确描述这些关联的能力。研究农药暴露的风险需要更多的数据，特别是描述特定淋巴癌亚型的风险-反应关系。我们建议进行一个强大的研究与职业农药暴露的风险，使用有效的方法相结合的现有数据资源，从10个病例对照研究参加了国际淋巴结联盟和国际多发性骨髓瘤联盟（IMMC）。汇总分析将包括超过11，000例病例和12，000例对照，以及有关工作历史，农业，作物，牲畜，农药使用，应用方法，个人防护设备和安全实践的详细问卷数据。我们的研究团队将为每种感兴趣的农药开发农药暴露矩阵（PEM），轴为职称，位置，年代，作物和livestoc。我们将应用环境监测模型进行暴露评估，然后审查每项研究的额外详细问卷数据，以确定每种农药的暴露概率和强度。我们将估计暴露于特定类型农药（例如，有机磷酸酯杀虫剂，拟除虫菊酯杀虫剂，苯氧基除草剂）和杀虫剂活性成分（例如，毒死蜱、二嗪农、马拉硫磷、氯菊酯、2，4-D、草甘膦），有患淋巴癌的风险。我们还将评估主要淋巴癌亚型之间估计农药暴露效应的异质性。InterLymph和IMMC联盟提供了一个出色的环境，以解决我们的研究目标，考虑到异常大量的病例和先前协调的病理学，职业和协变量的数据。我们在编码和协调参与研究的农药暴露变量方面的努力将为未来基于财团的研究开发宝贵的资源，例如农药暴露效应的基因-环境分析。

 DESCRIPTION (provided by applicant): Exposure to pesticides is widespread, both in certain jobs and at lower levels in the home environment. There is a strong need for data quantifying cancer risks from pesticides, both for elucidating toxicologic mechanisms of carcinogenesis and for supporting regulation. There are studies suggesting that certain current-use pesticides may increase risk of non-Hodgkin lymphoma (NHL) and other lymphoid cancers such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM); however the size of individual studies hinders the ability to describe these associations with precision. Much larger numbers are needed to study risks of pesticide exposures, particularly for describing exposure-response relationships and risks for specific lymphoid cancer subtypes. We propose to conduct a powerful study of the risks associated with occupational pesticide exposures using the efficient approach of combining existing data resources from 10 case-control studies participating in the InterLymph Consortium and International Multiple Myeloma Consortium (IMMC). The pooled analysis will include over 11,000 cases and 12,000 controls with detailed questionnaire data on job history, farming, crops, livestock, pesticide use, application methods, personal protective equipment, and safety practices. Our study team will develop pesticide exposure matrices (PEMs) for each pesticide of interest with axes for job title, location, decade, crop, and livestoc. We will conduct exposure assessment with application of the PEMs, followed by review of additional detailed questionnaire data from each study to refine exposure probability and intensity for each pesticide. We will estimate the association of exposure to specific types of pesticides (e.g., organophosphate pesticides, pyrethroid insecticides, phenoxy herbicides) and pesticide active ingredients (e.g., chlorpyrifos, diazinon, malathion, permethrin, 2, 4-D, glyphosate) with risk of lymphoid cancers. We will also evaluate heterogeneity in estimated pesticide exposure effects between major lymphoid cancer subtypes. The InterLymph and IMMC consortia offer an outstanding setting to address our study aims, given the exceptionally large number of cases and previously harmonized data on pathology, occupation and covariates. Our effort in coding and harmonizing pesticide exposure variables across participating studies will develop a valuable resource for future consortia-based research, such as gene-environment analyses of pesticide exposure effects.