MOLECULAR EPIDEMIOLOGY OF PROSTATE CANCER INTOBAGONIANS

来自加勒比多巴哥岛50-79岁非洲裔加勒比人口的初步前列腺癌筛查数据显示，PSA升高率很高（29%）（大于4ng/ml）。在接受活检的79%患者中，51%被诊断为前列腺癌。最近有报道说，非裔加勒比人的前列腺癌发病率很高。这些数据表明，在非裔美国人中观察到的前列腺癌风险升高，也存在于其他西非后裔人群中。这有力地表明，生活在不同环境中的非洲人后裔中，前列腺癌的风险受到遗传因素与生活方式/代谢因素的共同影响。我们建议在40-79岁的多巴哥男性人群（n=5121）（92%的非洲裔）中进行前列腺癌的分子流行病学研究。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50-79岁（n=3000）的人群。该研究将筛查40-49岁男性（n=1800） PSA升高（大于2ng/ml）或DRE异常，以及50-79岁男性。我们期望研究300例筛查发现的病例与300例频率年龄匹配的对照。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变异，或家族性前列腺癌1号和X号染色体的基因位点是否与前列腺癌相关，以及基因频率是否与已发表的白种人和非裔美国人人群的研究不同。其他分子标记将包括血清花生四烯酸和IGF-1（对于每一种，在病例中假设高水平）。骨密度（长期IGF-1和性激素暴露的替代指标）和中心脂肪分布将被测量（对于每一项，假设在某些情况下升高）。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，人口主要是西非裔，与非裔美国人相比，混合较少。了解环境、遗传和代谢因素的影响，将有助于采取措施降低美国、加勒比地区和其他地理区域的西非裔男性患前列腺癌的风险。

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.