Alcohol ingestion and colorectal neoplasia: a meta-analysis based on a Mendelian randomization approach.

Aim  Observed associations of alcohol with colorectal cancer are prone to distortion by confounding and reverse causation. A Mendelian randomization approach provides an unbiased estimate of the association using the aldehyde dehydrogenase 2 (ALDH2) variant as a surrogate of alcohol exposure. Method  A meta-analysis was performed to assess the association between the ALDH2 genotype and colorectal neoplasia, using the ALDH2 genotype as a marker of alcohol intake. Results  The pooled odds ratio (OR) of colorectal neoplasia was 1.31 (95%CI, 1.01–1.70) for the Glu/Glu vs the Lys/Lys genotype. There was no evidence of interstudy heterogeneity (P = 0.12, I2 = 42.7). The overall risk for Glu/Lys heterozygotes relative to Lys/Lys homozygotes (under a fixed-effects model) was 1.13 (95%CI, 0.86–1.48). There was no evidence of publication bias for Glu/Glu or Glu/Lys analysis. Conclusion  The result supports the role of alcohol in colorectal carcinogenesis based on a Mendelian randomization approach.