Abstract
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.
Highlights
Worldwide, prostate cancer ranks second in incidence rates and fifth in deaths from cancer among men.[1]
We evaluated the risks of 8 polymorphic sites in the promoter region/50 untranslated region (50UTR) of Cytochrome P450 1B1 (CYP1B1) for prostate cancer and how this is influenced by major lifestyle factors among a Caucasian population
The present study evaluated the risks of CYP1B1 polymorphisms in the promoter region/50UTR for prostate cancer and the influence of lifestyle factors in a Caucasian population
Summary
Prostate cancer ranks second in incidence rates and fifth in deaths from cancer among men.[1]. | 4677 identifying risks in the carcinogenesis process is an important step towards its prevention Lifestyle factors such as tobacco smoking and alcohol consumption are established risks for various types of cancers.[3,4] Worldwide, tobacco smoking accounts for roughly 21% of cancer deaths with 29% in high-income countries.[3] In the USA in the year 2010, the estimated death rate of all cancers due to cigarette smoking was roughly 38% with about 112 000 deaths among men aged 35 years or older and does not include additional deaths from environmental tobacco smoke or usage of cigars, pipes or smokeless tobacco.[5] In prostate, a meta-analysis of 4 million cohort participants showed that current cigarette smoking was correlated with increased risk of cancer death (relative risk [RR]; 1.24, 95% confidence interval [CI]; 1.18–1.31) with cigarettes smoked per day having a dose-response association with cancer mortality.[6] compared with non-smokers, former smokers (hazard ratio [HR]; 1.63, 95% CI; 1.30–2.04, P < .001) and current smokers (HR; 1.80, 95% CI 1.45–2.24, P < .001) had a higher risk of prostate cancer biochemical recurrence.[7]. We examined the functional effects of polymorphisms and have been suggested that minor alleles can affect promoter activity as well as correlate with protein expression in prostatic cells
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