Prostate cancer and pesticide exposure pilot study

描述（由申请人提供）： 有证据表明，接触杀虫剂可能与前列腺癌有关。职业与前列腺癌流行病学研究中农民的积极发现表明，农药可能参与前列腺癌的发生。尽管最近的农业和前列腺癌的荟萃分析报告的总体关联报告的总结相对风险为1.1是弱的，但大多数研究相对大量的受试者一致显示，农民，农场工人，农药制造商和施用者中前列腺癌的相对风险从1.06到5.0不等。这种来自病例对照研究的有限证据很可能是不确定的，因为难以测量农药暴露。已知的是，一些被归类为内分泌干扰化学品（EDCs）的农药会影响正常的激素功能。激素水平的变化会影响前列腺癌的风险，因为前列腺的正常生长取决于雄激素（性激素）水平的关键平衡。农药可能通过模仿激素、影响参与激素代谢的酶系统或直接影响参与激素功能的大脑区域来影响激素功能。 在加州的中央谷，全国领先的农药使用者，同时评估遗传和环境因素的前列腺癌在不同种族的人群不同的职业和住宅暴露于农药的大规模人群为基础的病例对照研究将有很长的路要走，以解决NCI的目标，进一步完善前列腺癌病因学的知识。然而，这种研究的复杂性要求有良好的试点数据和最大限度地利用现有接触评估数据的方法，以提高效率。一段时间以来，我们一直在评估农药使用报告（PUR）数据的使用情况，这些数据通过地理信息系统（GIS）中的土地使用补充数据进行了细化，以获得客观的历史农药暴露估计。 我们建议进行一项基于大型人群的病例对照研究的试点研究，该研究将解决以下两个目标： 1.显示与当前住宅和PUR/土地使用数据信息单独相比，历史住宅和PUR/土地使用数据在两种情况和对照中提供了暴露错误分类的显著减少 2.证明了在中央谷对前列腺癌的生化和环境危险因素（尤其是农药暴露）、易感基因及其相互作用进行病例对照研究的可行性。特别是，我们将证明我们的情况下选择方法的可行性，并获得颊DNA的遗传假设的方法。

DESCRIPTION (provided by applicant): There is some evidence that pesticide exposure might be related to prostate cancer. A possible involvement of pesticides in prostate carcinogenesis is suggested by positive findings for farmers in epidemiologic studies of occupation and prostate cancer. Although the overall association reported by recent meta-analyses of farming and prostate cancer reporting a summary relative risk of 1.1 is weak, the majority of studies with relatively large numbers of subjects consistently showed excess relative risks of prostate cancer ranging from 1.06 to 5.0 among farmers, farm laborers, pesticide manufacturers and applicators. This limited evidence from case-control studies may well be inconclusive because of the difficulty in measuring pesticide exposure. What is known is that some pesticides, classified as endocrine-disrupting chemicals (EDCs), can affect normal hormone function. Variations in hormone levels affect prostate cancer risk, since normal growth of the prostate gland is dependent on a critical balance of androgen (sex hormone) levels. Pesticides may affect hormone functioning by mimicking hormones, affecting enzyme systems involved in hormone metabolism, or directly affecting the brain regions involved in hormone functioning. A large-scale population-based case-control study in California's Central Valley, the nation's leading user of pesticides, simultaneously assessing genetic and environmental risk factors for prostate cancer in an ethnically-diverse population with varying occupational and residential exposures to pesticides would go a long way to addressing NCI's goals for further refining knowledge of prostate cancer etiology. However, the complexities of such a study warrant excellent pilot data and an approach that maximizes the use of existing exposure assessment data, for efficiency's sake. We have been evaluating for some time now the use of Pesticide Use Reporting (PUR) data, refined by additional data on land use, in a Geographical Information System (GIS) to obtain objective historical pesticide exposure estimates. We propose a pilot study for a large population-based case-control study that will address the following two aims: 1. show that historical residential and PUR/land use data provides substantial reduction in exposure misclassification in both cases and controls compared to current residential and PUR/land use data information alone 2. demonstrate the feasibility of conducting a case-control study of biochemical and environmental risk factors (especially pesticide exposure), susceptibility genes, and their interactions for prostate cancer in the Central Valley. In particular, we will demonstrate the feasibility of our case selection method, and methods of obtaining buccal DNA for genetic hypotheses.