Bangsi Dieudonne, Zhou Junying, Sun Yezhou, Patel Nimesh P, Darga Linda L, Heilbrun Lance K, Powell Isaac J, Severson Richard K, Everson Richard B
Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Urol Oncol. 2006 Jan-Feb;24(1):21-7. doi: 10.1016/j.urolonc.2005.09.005.
Genes involved in androgen metabolism are strong candidates for having an important role in the pathogenesis of prostate cancer. CYP3A4, a protein in the cytochrome P-450 supergene family, facilitates the oxidative deactivation of testosterone. In previous studies, patients with the G variant of a genetic polymorphism in CYP3A4 had prostate cancers with clinically aggressive characteristics at diagnosis. The association was strongest among elderly men. We investigated whether the CYP3A4 variant was linked with the diagnosis or clinical presentation of prostate cancer in a case control study of a multiethnic urban population. Biologic specimens were genotyped for CYP3A4, and analyzed for the impact of this genotype on risk and tumor characteristics at presentation, controlling for the effect of several cofactors. The CYP3A4 variant was more common among African-Americans than among white men. Race-stratified analyses revealed little association between the CYP3A4 variant and prostate cancer risk among white men but were limited by the small number of white men with the CYP3A4 variant. Of African-American men, while the variant G allele was not associated with prostate cancer that had less aggressive characteristics, it was associated with risk of aggressive prostate cancer when men with the AG genotype (odds ratio = 9.3, 95% confidence interval 1.3-411) or GG genotype (odds ratio = 11.9 95% confidence interval 1.6-533) were compared with those with the AA genotype. The association between the CYP3A4 genotype and aggressive prostate cancer in African-American men is consistent with findings of other studies.
参与雄激素代谢的基因极有可能在前列腺癌的发病机制中发挥重要作用。细胞色素P - 450超基因家族中的一种蛋白质CYP3A4，可促进睾酮的氧化失活。在以往研究中，携带CYP3A4基因多态性G变体的患者在诊断时患有具有临床侵袭性特征的前列腺癌。这种关联在老年男性中最为明显。我们在一项针对多民族城市人群的病例对照研究中，调查了CYP3A4变体是否与前列腺癌的诊断或临床表现相关。对生物样本进行CYP3A4基因分型，并分析该基因型对发病时风险和肿瘤特征的影响，同时控制几个辅助因子的作用。CYP3A4变体在非裔美国人中比在白人男性中更常见。种族分层分析显示，CYP3A4变体与白人男性前列腺癌风险之间几乎没有关联，但因携带CYP3A4变体的白人男性数量较少而受到限制。在非裔美国男性中，虽然G变体等位基因与侵袭性较小的前列腺癌无关，但当将AG基因型（比值比 = 9.3，95%置信区间1.3 - 411）或GG基因型（比值比 = 11.9，95%置信区间1.6 - 533）的男性与AA基因型的男性进行比较时，它与侵袭性前列腺癌的风险相关。非裔美国男性中CYP3A4基因型与侵袭性前列腺癌之间的关联与其他研究结果一致。
