EPIDEMIOLOGY OF PROSTATE CANCER--ODC AND AR GENOTYPES

为了与NCI的倡议保持一致，以促进对前列腺癌起源和发展的创新分子流行病学研究，我们计划重点研究在鸟氨酸脱羧酶基因(ODC)上发现的一种新的多态性与前列腺癌发展之间的联系。鸟氨酸脱羧酶(ODC)是多胺生物合成途径中的一种酶，负责细胞的增殖和分化。ODC的过度表达被证明是肿瘤生长和进展的易感基因。我们还计划探索ODC基因和前列腺癌风险之间的关联是否因雄激素受体基因的多态而不同。这项嵌套病例对照研究将使用诊断前采集的血液以及和1996年从华盛顿县男性收集的两份独立问卷的信息，作为正在进行的大型前瞻性研究的一部分。164名患有前列腺癌的患者将与323名年龄、性别匹配且在确诊时未患其他癌症的对照组进行比较。从病因学的角度来看，这些发现将有助于理解影响前列腺癌男性肿瘤生长和进展的遗传因素。从预防的角度来看，我们可能能够分离出一组患前列腺癌风险较高的男性，并可能通过使用已被证明抑制鸟氨酸脱羧酶的药物，如α-二氟甲基鸟氨酸(DFMO)或绿茶来改变这种风险。

In keeping with the NCI initiative to stimulate innovative molecular epidemiologic research into the origins and progression of prostate cancer we plan to focus on the association between a new polymorphism found on the ornithine decarboxylase gene (ODC) and the development of prostate cancer. Ornithine Decarboxylase (ODC) is an enzyme in the polyamine biosynthetic pathway responsible for cellular proliferation and differentiation. Overexpression of ODC has been shown to predispose to both tumor growth and progression. We also plan to explore whether the association between the ODC genotype and the risk of prostate cancer varies by the presence of a polymorphism of the androgen receptor gene. This nested case-control study will be conducted using pre- diagnostic blood collected in 1989 as well as information on two separate questionnaires collected from men in Washington County in 1989 and 1996 as part of a large ongoing prospective study. 164 cases who have developed prostate cancer will be compared with 323 controls that are matched on age, gender and were free of other cancers at the time of diagnosis of the case. From the point of view of etiology, findings will aid in the understanding of inherited factors that influence tumor growth and progression in men with prostate cancer. From the point of view of prevention, we may be able to isolate a group of men that are at a higher risk of developing prostate cancer and possibly modify this risk by using drugs such as alpha- difluoromethylornithine (DFMO) or green tea that have been shown to inhibit ornithine decarboxylase.