EPIDEMIOLOGY OF PROSTATE CANCER--ODC AND AR GENOTYPES

为了与NCI倡议保持一致，我们计划将重点放在鸟氨酸脱羧酶基因（ODC）上新发现的多态性与前列腺癌发展之间的关系。鸟氨酸脱羧酶（Ornithine Decarboxylase， ODC）是多胺生物合成途径中负责细胞增殖和分化的一种酶。ODC的过表达已被证明易导致肿瘤的生长和进展。我们还计划探讨ODC基因型与前列腺癌风险之间的关系是否因雄激素受体基因多态性的存在而变化。这项巢式病例对照研究将使用1989年收集的诊断前血液以及1989年和1996年从华盛顿县收集的两份独立问卷的信息进行，这是一项正在进行的大型前瞻性研究的一部分。164名前列腺癌患者将与323名在年龄、性别上匹配且在诊断时没有其他癌症的对照组进行比较。从病因学的角度来看，研究结果将有助于了解影响前列腺癌患者肿瘤生长和进展的遗传因素。从预防的角度来看，我们可能能够隔离出一组患前列腺癌风险较高的男性，并可能通过使用α -二氟甲基鸟氨酸（DFMO）或绿茶等药物来降低这种风险，这些药物已被证明可以抑制鸟氨酸脱羧酶。

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.