A critical analysis of the relationship between aldehyde dehydrogenases-2 Glu487Lys polymorphism and colorectal cancer susceptibility

Studies investigating the association between genetic polymorphism of aldehyde dehydrogenases-2 (ALDH-2) Glu487Lys and colorectal cancer (CRC) risk have reported conflicting results. Given this uncertainty, we carried out a critical analysis of published case-control studies to derive a more precise estimation of this relationship. Published literature from PubMed, EMBASE and China Knowledge Resource Integrated Database were retrieved, and the literature search was updated in June 2014. Eleven studies comprising 6965 subjects were selected (2300 cases and 4665 controls). Overall, our study showed no statistical significance for CRC risk associated with any of the genetic models of ALDH-2 Glu487Lys polymorphism. When studies were stratified for control source, a decreased risk of CRC for participants with Lys/Lys was observed in population based case-control studies [Lys/Lys vs. (Glu/Lys + Glu/Glu): odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.38-0.87]. Furthermore, we also confirmed the significant correlation between Glu487Lys polymorphism and the influence on the risk of rectal cancer in males [Glu/Glu vs. (Glu/Lys + Lys/Lys): OR = 1.52, 95%CI = 1.10-2.08]. The combined effects of the two gene polymorphisms [ALDH-2 and alcohol dehydrogenase 1B (ADH-1B)] were also studied. Compared with subjects having ALDH-2 Lys+ with ADH-1B His/His, ORs and 95%CIs for those with ALDH-2 Glu/Glu and ADH-1B His/His was 3.42(0.57-20.38). Similar trends were observed for the other two types of comparisons. Our study supports that ALDH-2 Glu487Lys polymorphism is associated with significant reduced risks of CRC in population-based samples, and of rectal cancer in males.