Genetic Susceptibility to Cancers of the Prostate and Urinary Bladder

描述(由申请人提供)：项目摘要：这项拟议研究的总体目标是在两项既定研究中评估遗传因素对前列腺癌和膀胱癌风险的影响，这两项研究的选择是因为它们独特的设计和方法，以及候选人对这两项研究人群的经验和熟悉程度。第一个目标将集中在参加前列腺癌遗传学项目的患有遗传性前列腺癌的非裔美国男性。我们将对最近的一项发现进行后续调查，该发现表明，在参与这项旨在定位一个或多个前列腺癌易感基因的大型家庭研究中，非裔美国人家庭中存在22号染色体上的关联。我们还计划制定新的招募战略，以增加非裔美国人家庭的参与，以更全面地描述患有遗传性前列腺癌的非裔美国人的临床和基因特征。该项目的第二个目标是研究砷介导的膀胱癌风险的遗传修饰物。我们已经提议调查几个被怀疑影响无机砷甲基化和膀胱癌风险的候选基因之间的关联。我们将与新英格兰环境与健康研究的合作者共同收集数据，以评估基因和砷暴露的单独和联合影响。这项研究计划主要涉及使用传统的基因分析方法来探索基因研究的新领域，再加上拟议的正规遗传学课程和遗传学实验室的经验，将有助于广泛发展癌症流行病学家的基因培训，她计划将自己的研究生涯致力于泌尿系癌症的研究。相关性：前列腺癌和膀胱癌是美国诊断出的两种最常见的癌症，有强有力的证据表明，遗传易感性是这两种癌症发生的重要因素。确定具有遗传易感性的个人对于制定初级预防和/或早期发现疾病的战略将是重要的。

DESCRIPTION (provided by applicant): Project Summary: The overall goal of this proposed research is to estimate the effects of genetic factors on risk of prostate and bladder cancers in two established studies chosen for their distinct design and methodology as well as the candidate's experience and familiarity with the two study populations. The first aim will focus on African American men with inherited forms of prostate cancer participating in the Prostate Cancer Genetics Project. We will perform follow-up investigations of a recent finding suggesting linkage on chromosome 22 among African American families participating in this large family-based study designed to localize one or more prostate-cancer susceptibility genes. We also plan to develop new recruitment strategies to increase participation of African American families to more fully characterize the clinical and genetic characteristics of African Americans with hereditary prostate cancer. The second aim of the project focuses on genetic modifiers of arsenic-mediated bladder cancer risk. We have proposed to investigate the association of several candidate genes that are suspected of influencing the methylation of inorganic arsenic and bladder-cancer risk. We will pool our data with collaborators from the New England Study of Environment and Health to estimate the separate and joint effects of genotype and arsenic exposure. This research plan, which involves the use of largely traditional approaches of genetic analysis to explore novel areas of genetic research, coupled with the proposed formal genetic coursework and experience in a genetics laboratory will serve to broadly develop the genetic training of a cancer epidemiologist who plans to devote her research career to the study of urologic cancers. Relevance: Cancers of the prostate and urinary bladder are two of the most common cancers diagnosed in the United States with strong evidence that genetic susceptibility is an important factor in the development of both cancers. Identifying individuals with an inherited predisposition would be important in developing strategies for the primary prevention and or early detection of disease.