polymorphisms, occupational and environmental exposures and risk of bladder cancer

International audienceCytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5′-noncoding promoter region of gene [mainly −(rs35694136) and −(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between − (or −) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (≥50 packyears; OR 5.6, 95% CI: 2.5-12.5) and heavy coffee drinkers (>5 cups/day; OR 3.1, 95% CI: 1.2-7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) ( = 0.04), with heavy smoking as possible confounder A decreased risk was noted for large leaf vegetable consumption, with significant trend from 3 times/week ( = 0.008). The case-only analysis showed an interaction between − and tobacco smoking >25 packyears ( = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with − genotype as well as no overall effect of by itself on BC risk. This is the first study suggesting that modifies the effect of cigarette smoking on BC risk

<it>CYP1A2</it> rs762551 polymorphism contributes to cancer susceptibility: a meta-analysis from 19 case-control studies

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphism (rs762551A>C) in gene encoding cytochrome P450 1A2 (<it>CYP1A2</it>) has been shown to influence the inducibility of <it>CYP1A2</it> expression and thus might be associated with risk of several types of human cancer. However, the results of previous studies on the associations of this polymorphism with risk of cancer are not all consistent. To clarify the potential contribution of <it>CYP1A2</it> rs762551 to cancer risk, we performed a meta-analysis of the published case–control studies.</p> <p>Methods</p> <p>We used PubMed, Embase, OVID, ScienceDirect, and Chinese National Knowledge Infrastructure databases to identify the related publications for this meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random effect model to evaluate the association of rs762551 with cancer risk. A <it>χ</it>²-based Q-test was used to examine the heterogeneity assumption and the funnel plot and Egger’s test were used to examine the potential publication bias. The leave-one-out sensitivity analysis was conducted to determine whether our assumptions or decisions have a major effect on the results of the review.</p> <p>Results</p> <p>Our analysis of 19 eligible case–control studies showed a significant association between rs762551C variant with risk of cancer in the genetic model of CC versus AA (OR = 1.30, 95% CI = 1.02-1.64) and the dominant model (OR = 1.19, 95% CI = 1.04-1.36). In subgroup analysis based on ethnicity, the rs762551CC genotype was associated with increased cancer risk (OR = 1.29, 95% CI = 1.27-1.63 in co-dominate model and OR = 1.17, 95% CI = 1.02-1.34 in dominant model in Caucasians, but not in Asians and the mixed population.</p> <p>Conclusion</p> <p>These results suggested that <it>CYP1A2</it> rs762551 polymorphism is likely to be associated with susceptibility to cancer in Caucasians.</p