Abstract 1242: Differences of cytochrome P450 1B1 polymorphisms on prostate cancer risk between races

Abstract

Abstract Prostate cancer is the most common cancer among men in the United States but when comparing between races, rates are much higher in African-Americans (AfA) compared to Caucasians (Cau). Reasons for this discrepancy are unknown but studies have shown that polymorphisms of cytochrome P450 1B1 (CYP1B1), a gene that activates carcinogens, to be involved in prostate cancer pathogenesis. In this study, how race influences CYP1B1 polymorphisms and prostate cancer risk were investigated. Blood genomic DNA from a Cau (469 controls, 500 prostate cancer), AfA (152 controls, 218 cases) and Japanese (JPN) (131 controls, 177 cases) population were obtained. Eight polymorphic sites of the promoter or 5'-untranslated region of CYP1B1 (rs2551188 G to A, rs2567206 C to T, rs2567207 T to C, rs162556 T to C, rs10175368 G to A, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed using Taqman genotyping assays and sequence-specific PCR, and genotyping results tabulated. Also, CYP1B1 protein expression was determined in 52 Cau benign prostatic hyperplasia specimens and levels categorized by polymorphic sites. Racial differences for prostate cancer risk due to CYP1B1 polymorphisms were observed. In Cau, minor alleles rs2551188 A, rs2567206 T and rs10175368 A showed increased risk for cancer (P<0.05). Linkage was observed between rs2551188-rs2567206-rs2567207-rs10175368 and the major G-C-T-G haplotype was reduced in cancer cases (P<0.001). Interestingly when analyzing prostatic tissue specimens, minor genotypes of rs2551188 (P<0.05), rs2567206 (P<0.05) and rs10175368 (Ptrend=0.065) displayed higher levels and major G-C-T-G haplotype lower levels (P<0.05) of CYP1B1 protein expression, which were consistent with genotyping results. For AfA, minor rs2551188 A allele decreased risk for prostate cancer (P<0.001). Rs163090-rs162331 were linked and the minor A-G haplotype displayed a reduced prostate cancer risk (P<0.05). Among JPN, minor rs2567206 T allele also reduced cancer risk (P<0.05). Two sets of linkages, rs2551188-rs2567206-rs2567207-rs162556-rs10175368 and rs163090-rs162330-rs162331 were observed and the minor A-T-C-T-A and major A-T-A haplotypes respectively, showed a decreased risk for cancer (P<0.01). These results suggest a differential effect of CYP1B1 polymorphisms for prostate cancer risk between races and these results are important in understanding its role in this disease. Citation Format: Taku Kato, Yutaka Hashimoto, Ryan Wong, Yozo Mitsui, Shigekatsu Maekawa, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Laura Tabatabai, Hiroaki Shiina, Rajvir Dahiya, Takashi Deguchi, Yuichiro Tanaka. Differences of cytochrome P450 1B1 polymorphisms on prostate cancer risk between races [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1242.