GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER

描述(摘自申请者的摘要)：可能发生前列腺癌 涉及遗传性遗传易感性和 外源性和内源性暴露。根据我们目前对 前列腺癌的发生，我们提出了一项仅病例/病例对照的混合研究 旨在衡量假定的遗传和环境的联合影响 风险因素。我们计划招募440例70岁以下的前列腺癌患者 以及220名种族和年龄频率匹配的健康对照组。这项研究将是 在白人和高加索人之间平均分配的人群中进行 非洲裔美国人，这样特定种族的风险因素和互动可以 已确认身份。我们研究的主要目标是：1)确定是否选择了 职业(即镉、锌和多环烃)、环境 (即饮食、紫外线辐射)、生活方式(即体力活动)和 遗传(即，CYP17、CYP3A4、GSTP1、SRD5A2、维生素D受体、雄激素 受体、金属硫蛋白2A、HSD3B2基因多态性)危险因素相关 前列腺癌风险增加；以及2)测试 上述遗传和环境风险因素可能与基因-环境和 基于它们在前列腺癌发生中的定位作用的基因-基因相互作用。 在我们的研究设计中包括控件将使我们能够估计主要 影响并测试遗传和环境风险因素是否 独立自主。如果是后者，那么我们可以使用更大的案例样本来 基于生物学可能性的特定基因-环境相互作用的测试 场景。分析将使用对数线性模型进行，该模型 唯一地允许我们根据我们的 具体的分析目标(例如，估计主要影响与相互作用 条款)。这项研究将是已知的第一项专门设计用来测试 用于前列腺癌发生中的基因-环境相互作用。

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.