title: 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.
abstract: 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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hygienic Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jinyi
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yuan
authors.forename: Ketaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takezaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial