In conclusion, our study found that genetic predisposition to alcohol drinking was causally associated with increased CRC risk and the pathogenic effect of alcohol could be partly attributed to DNA methylation via regulating the expression of COLCA1/COLCA2 gene; the eQTL rs3087967 and mQTL rs11213823 polymorphism of COLCA1/COLCA2 gene would interact with alcohol consumption to increase the risk of CRC. This evidence concerns the gene COLCA1 and colorectal carcinoma.