Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals
Menée en population danoise auprès de 47 089 participants, cette étude évalue l’association entre des polymorphismes du gène EPHX1 et le risque de cancers liés au tabac
Background: Two functional polymorphisms of the microsomal epoxide hydrolase gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered microsomal epoxide hydrolase activity affects risk of cancer in the general population. Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene, and divided them into groups with predicted fast, intermediate, and slow microsomal epoxide hydrolase activity. Using Cox proportional hazards models, we calculated hazard ratios for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers. Results: Of the 47,089 individuals, 7590 experienced a cancer event, and of these, 1466 were tobacco-related. After multifactorial adjustment, the hazard ratios (95% confidence interval) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow microsomal epoxide hydrolase activity vs. individuals with the fast phenotype (p for trend = 0.003). The corresponding hazard ratios among eversmokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) (p for trend = 0.003), while hazard ratios among neversmokers did not differ from 1.0. Conclusions: Our results indicate that genetically lowered microsomal epoxide hydrolase activity is associated with increased risk of tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.