MOLECULAR EPIDEMIOLOGY OF PROSTATE CANCER IN TOBAGONIANS

来自加勒比海托巴哥岛上50-79岁的加勒比黑人人群的初步前列腺癌筛查数据显示，PSA升高（大于4 ng/ml）的比率很高（29%）。 在79%接受活检的患者中，51%被诊断患有前列腺癌。 据报告，牙买加非洲裔加勒比人前列腺癌发病率很高。这些数据表明，在非洲裔美国人中观察到的前列腺癌风险升高存在于西非血统的其他人群中。 这有力地表明，前列腺癌的风险受到遗传成分以及生活在不同环境中的非洲裔人群中常见的生活方式/代谢因素的影响。 我们建议在托巴哥男性人群中进行前列腺癌的分子流行病学研究，年龄在40-79岁（n=5121），（92%的非洲裔）。 我们目前正在使用血清（前列腺特异性抗原）PSA（大于4 ng/ml）和直肠指检（DRE）筛查年龄在50-79岁（n=3000）的人群。 除了50-79岁的男性外，这项拟议的研究还将筛选40-49岁的男性（n=1800）是否有PSA升高（大于2ng/ml）或DRE异常。 我们希望研究300例筛查发现的病例，并与300例频率年龄匹配的对照进行比较。 我们将确定与性激素代谢、生长因子、维生素D、PSA转运和有毒物质代谢相关的候选基因的变异，或与1号和X号染色体家族性前列腺癌基因座相关的候选基因的变异是否与前列腺癌相关，以及基因频率是否与已发表的高加索人和非洲裔美国人的研究不同。 其他分子标志物将包括血清花生四烯酸和IGF-1（对于每一种，假设病例中的高水平）。 将测量骨矿物质密度（长期IGF-1和性激素暴露的替代物）和中心脂肪分布（对于每种情况，假设病例升高）。 这个庞大的、非常合作的西非裔男性群体为前列腺癌风险的研究提供了一个独特的机会，因为前列腺癌风险很高，该群体主要是西非裔，并且与非洲裔美国人相比混合较少。 了解环境、遗传和代谢因素的作用将有助于采取措施降低美国西非裔男性患前列腺癌的风险，加勒比和其他地理区域。

Preliminary prostate cancer screening data from the Afro- Caribbean population aged 50-79 on the Caribbean island of Tobago revealed a high rate (29 percent) of elevated PSA (greater than 4ng/ml). Of the 79 percent undergoing biopsy, 51 percent were diagnosed with prostate cancer. High incidence of prostate cancer has recently been reported among Afro-Caribbean Jamaicans. These data suggest that the elevated risk for prostate cancer, observed in African Americans, is present in other populations of West African descent. This strongly suggests that prostate cancer risk is influenced by genetic component(s) in combination with lifestyles/metabolic factors common across populations of African descent living in diverse environments. We propose to conduct a molecular epidemiology study of prostate cancer in the Tobago male population, aged 40-79 (n=5121), (92 percent of African descent). We are currently screening the population, aged 50-79 (n=3000) using serum (prostate specific antigen) PSA (greater than 4 ng/ml) and digital rectal exam (DRE). This proposed study will screen men aged 40-49 (n=1800) for elevated PSA (greater than 2ng/ml) or abnormal DRE, in addition to men aged 50-79. We expect to study 300 screening detected cases compared with 300 frequency age matched controls. We will determine whether variants in candidate genes related to sex hormone metabolism, growth factor, vitamin D, PSA transport and toxic substance metabolism, or to loci for familial prostate cancer of chromosomes 1 and X, are associated with prostate cancer, and whether gene frequencies differ from published studies of Caucasian and African American populations. Other molecular markers will include serum arachidonic acid and IGF-1 (for each, hypothesize high levels in cases). Bone mineral density, a surrogate for long term IGF-1 and sex hormone exposure, and central fat distribution will be measured (for each, hypothesize elevated in cases). This large, very cooperative, male population of West African descent, provides a unique opportunity for the study of prostate cancer risk because prostate cancer risk is high, the population is primarily of West African descent, and there is less admixture than among African Americans. Understanding the contribution of environment, genetic and metabolic factors will lead to measures to reduce the risk for prostate cancer among men of West African descent in the U.S., the Caribbean and other geographic areas.