GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER

描述（改编自申请人摘要）：可能为前列腺癌 涉及遗传易感性和 外源性和内源性暴露。根据我们目前对 前列腺癌的发生，我们提出了一个混合病例/病例对照研究 旨在测量假定的遗传和环境的联合影响， 危险因素我们计划招募440例70岁以下的前列腺癌病例 和220名种族和年龄频率匹配的健康对照。本研究将 在白人和白人之间平均分配的人群中进行 非裔美国人，以便种族特定的风险因素和相互作用可以 鉴定本研究的主要目的是：1）确定是否选用 职业（即，镉、锌和多环碳氢化合物），环境 (i.e.,饮食，紫外线辐射），生活方式（即，体力活动）和 遗传的（即，CYP 17、CYP 3A 4、GST P1、SRD 5A 2、维生素D受体、雄激素 受体，金属硫蛋白2A，HSD 3B 2多态性）的危险因素相关 前列腺癌的风险增加;和2）测试 上述遗传和环境风险因素为假定的基因-环境和 基因-基因相互作用的基础上，其假定的作用，在前列腺癌。 在我们的研究设计中纳入对照将使我们能够估计主要的 影响，并测试遗传和环境风险因素是否 独立的如果后者是真的，那么我们可以使用更大的案例样本， 基于生物学合理性的特定基因-环境相互作用的测试 场景将使用对数线性模型进行分析， 唯一允许我们根据我们的 特定的分析目标（例如，主效应与相互作用的估计 条款）。这项研究将是已知的第一个专门设计用于测试 前列腺癌发生中基因与环境的相互作用。

DESCRIPTION (Adapted from applicant's abstract): Prostate carcinogenesis likely involves a complex interplay between inherited genetic susceptibility and exogenous and endogenous exposures. Based on our current understanding of prostate carcinogenesis, we propose a hybrid case-only/case-control study designed to measure the joint effects of putative genetic and environmental risk factors. We plan to enroll 440 incident prostate cancer cases under age 70 and 220 race and age frequency-matched healthy controls. This study will be carried out in a population evenly divided between Caucasians and African-Americans, so that race-specific risk factors and interactions can be identified. The main goals of our study are: 1) to determine whether selected occupational (i.e., cadmium, zinc and polycyclic hydrocarbons), environmental (i.e., diet, ultraviolet radiation), lifestyle (i.e., physical activity) and genetic (i.e., CYP17, CYP3A4, GSTP1, SRD5A2, vitamin D receptor, androgen receptor, metallothionein 2A, HSD3B2polyhmorphisms) risk factors are associated with increased risk for prostate cancer; and 2) to test combinations of the above genetic and environmental risk factors for putative gene-environment and gene-gene interactions based on their posited role in prostate carcinogenesis. The inclusion of controls in our study design will allow us to estimate main effects and test whether genetic and environmental risk factors are independent. If the latter is true, then we can use our larger case sample to test for specific gene-environment interactions based on biologically plausible scenarios. The analysis will be conducted using log-linear models, which uniquely allow us to include or exclude control data depending upon our specific analytic goals (e.g., estimation of main effects vs. interaction terms). This study will be the first known effort specifically designed to test for gene-environmental interaction in prostate carcinogenesis.