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Influence of lifestyle choices on risks of CYP 1B1 polymorphisms for prostate cancer
Author(s) -
Kato Taku,
Hashimoto Yutaka,
Wong Ryan K.,
Mitsui Yozo,
Maekawa Shigekatsu,
Chang Inik,
Shahryari Varahram,
Yamamura Soichiro,
Majid Shahana,
Saini Sharanjot,
Tabatabai Z. Laura,
Dahiya Rajvir,
Deguchi Takashi,
Tanaka Yuichiro
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13696
Subject(s) - prostate cancer , minor allele frequency , genotype , genotyping , allele , biology , cancer , haplotype , genetics , cyp1b1 , population , carcinogen , biomarker , taqman , oncology , medicine , allele frequency , gene , cytochrome p450 , endocrinology , real time polymerase chain reaction , environmental health , metabolism
Cytochrome P450 1B1 ( CYP 1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP 1B1 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 CYP 1B1 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 CYP 1B1 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 CYP 1B1 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.

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