Department of Urology, Veterans Affairs Medical Center, San Francisco, CA, USA.
Department of Urology, University of California, San Francisco, CA, USA.
J Cell Mol Med. 2018 Oct;22(10):4676-4687. doi: 10.1111/jcmm.13696. Epub 2018 Aug 22.
Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5' untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer. Linkage was observed between rs2551188, rs2567206, rs2567207 and rs10175368, and the G-C-T-G haplotype (major allele at respective sites) was decreased in cancer. Interestingly when classified by lifestyle factors, no associations of genotypes were found for non-smokers and non-drinkers, whereas on the contrary, minor type at rs2567206 and rs10175368 increased and major G-C-T-G decreased risk for cancer among smokers and drinkers. Interestingly, rs2551188, rs2567206 and rs10175368 minor genotypes correlated with increased tissue CYP1B1 as determined by immunohistochemistry. Further, rs10175368 enhanced luciferase activity and mobility shift show stronger binding of nuclear factor for the minor allele. These results demonstrate smoking and alcohol consumption to modify the risks of CYP1B1 polymorphisms for prostate cancer which may be through rs10175368, and this is of importance in understanding their role in the pathogenesis and as a biomarker for this disease.
细胞色素 P450 1B1（CYP1B1）将外来物质转化为致癌物质，以及生活方式的选择如何与 CYP1B1 多态性相互作用并影响前列腺癌风险，对此进行了评估。使用 TaqMan 基因分型检测，分析了来自白种人群的血液基因组 DNA 在 CYP1B1 的 5'非翻译区的多态性位点。总体而言，饮酒状态和 rs2551188、rs2567206 和 rs10175368 中的次要等位基因与前列腺癌有关。rs2551188、rs2567206、rs2567207 和 rs10175368 之间观察到连锁，并且在癌症中减少了 rs10175368 中相应位点的主要等位基因的 G-C-T-G 单倍型。有趣的是，当按生活方式因素分类时，非吸烟者和非饮酒者的基因型没有关联，而相反，rs2567206 和 rs10175368 的次要类型增加了吸烟者和饮酒者的癌症风险，而主要 G-C-T-G 降低了风险。有趣的是，rs2551188、rs2567206 和 rs10175368 的次要基因型与免疫组织化学测定的组织 CYP1B1 增加相关。此外，rs10175368 增强了荧光素酶活性和迁移率变化，表明核因子对次要等位基因的结合更强。这些结果表明，吸烟和饮酒会改变 CYP1B1 多态性对前列腺癌的风险，这可能是通过 rs10175368 实现的，这对于理解它们在发病机制中的作用以及作为该疾病的生物标志物非常重要。
