title: Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer.
abstract: BACKGROUND
  In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer.
  
  
  METHODS
  A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken.
  
  
  RESULTS
  Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls.
  
  
  CONCLUSIONS
  In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.
authors.affiliation: Department of Epidemiology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. kvisvana@jhsph.edu
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Crum
authors.forename: Paul T
authors.initials: PT
authors.lastname: Strickland
authors.forename: Xiaojun
authors.initials: X
authors.lastname: You
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Hoffman
authors.forename: George W
authors.initials: GW
authors.lastname: Comstock
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
mesh_terms: D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000426:Alcohol Dehydrogenase