Article

A Novel Polymorphism rs1329149 of CYP2E1 and a Known Polymorphism rs671 of ALDH2 of Alcohol Metabolizing Enzymes Are Associated with Colorectal Cancer in a Southwestern Chinese Population

Department of Hygienic Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 09/2009; 18(9):2522-7. DOI: 10.1158/1055-9965.EPI-09-0398
Source: PubMed

ABSTRACT 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.
A hospital-based case-control study of 440 CRC patients and 800 cancer-free controls was conducted. Personal information was collected by a Semi-Quantitative 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.
Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus rs1329149 and a known ALDH2 locus rs671 were found to be significantly associated with CRC risk. The adjusted OR was 1.86 (95% CI, 1.12-3.09) for the rs671 A/A genotype and 4.04 for the rs1329149 T/T genotype (95% CI, 2.44-6.70), compared with their common homozygous genotypes. Interaction was found between alcohol consumption and gene polymorphisms on CRC, the adjusted OR was 7.17 (95% CI, 2.01-25.53) for drinking habits combined with rs671 A/A or rs1329149 T/T genotype.
The results of this study suggest that rs671 A/A and the first reported locus rs1329149 T/T genotypes increase the susceptibility to CRC, and gene-environmental interaction between the two loci and alcohol use existed for CRC in Southwestern Chinese. Larger studies are warranted to verify our findings.

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    • "Selected Asian populations have higher frequencies of ADH1B*2 and ALDH2*2 mutant alleles (up to 40%) than Caucasians (<5%) [34]. ADH1B and ALDH2 polymorphisms have been related to the risk of selected cancers, particularly of the upper aerodigestive tract, in alcohol drinkers [35] [36] [37] of Asian descendents, while studies conducted in European populations found no significant association with ADH1B*1, whereas practically all Europeans were homozygous for ALDH2*1 [38]. However, since we identified only four studies from Asia [6] [13] [16] [17], this finding needs further confirmation. "
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    • "Chiang's study [15] found that the allele frequency of ALDH2 A was significantly higher in colorectal cancer cases; however, Miyasaka's study[16] found that the A/A genotype of ALDH2 might not be a risk factor for colorectal cancer. Yang's study [17] found that the ALDH2 A/A genotype could increase susceptibility to CRC (adjusted OR = 1.86 (95% CI, 1.12–3.09)); however, Yin's study [19] discovered that the ALDH2A/A genotype was related to a statistically significantly decreased risk of colorectal cancer (adjusted OR 0.55, 95% CI  =  0.33–0.93). "
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