Background: To screen for tagging single nucleotide polymorphisms (tagSNP) in the major alcohol metabolizing enzymes: ADH1B, ALDH2, and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population. Methods: A hospital-based case-control study of 440 CRC patients and 800 cancer-free controls was conducted. Personal information was collected by a SemiQuantitative Food Frequency Questionnaire. The tagSNPs were screened in the HapMap with Haploview by setting the minor allele frequency at 0.03 with the highest score of r 2 form each block. Genotypes were identified by using the SNPLex System. Both crude and adjusted odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risk of each SNP. Results: Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus