CYP1B1 genotype and risk of cardiovascular disease, pulmonary disease, and cancer in 50,000 individuals.

摘要

OBJECTIVE: Cytochrome P450 (CYP) 1B1 enzymes metabolize tobacco-smoke polycyclic aromatic hydrocarbons and 17beta-estradiol. CYP1B1*3 (rs1056836 = Leu432Val = 4326C>G) and CYP1B1*4 (rs1800440 = Asn453Ser = 4390A>G) influence this metabolism. We, therefore, hypothesized that these two polymorphisms associate with risk of myocardial infarction (MI), ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), chronic obstructive pulmonary disease (COPD), cancer overall, tobacco-related cancer, and female cancer, possibly dependent on tobacco exposure. METHOD: We genotyped 10 391 adults from the Copenhagen City Heart Study, who had been followed prospectively for more than 30 years. Significant results were retested cross-sectionally in the Copenhagen General Population Study (CGPS) with 37 178 participants, and in the Copenhagen Ischemic Heart Disease Study with 2379 cases and 33 220 controls. RESULTS: In the Copenhagen City Heart Study, hazard ratio for MI among never smokers was 1.9 (95% confidence interval: 1.2-3.2) for CYP1B1*3 GG (19%) versus CC (32%). These findings were, however, not confirmed when retested in CGPS and Copenhagen Ischemic Heart Disease Study. For tobacco-related cancer, we found decreasing risk with CYP1B1*3 CG and GG versus CC; however, this could not be confirmed in the CGPS. For IHD, ICVD, COPD, cancer overall, and female cancer, we found no association with CYP1B1*3 genotype, overall or according to smoking status. For CYP1B1*4 genotype, we did not find any association with either endpoint, overall or according to smoking status. CONCLUSION: CYP1B1*3 and CYP1B1*4 genotypes did not associate with the risk of MI, IHD, ICVD, COPD, cancer overall, tobacco-related cancer, or female cancer.