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Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer.

Authors
Visvanathan-K; Crum-RM; Strickland-PT; You-X; Ruczinski-I; Berndt-SI; Alberg-AJ; Hoffman-SC; Comstock-GW; Bell-DA; Helzlsouer-KJ
Source
Alcohol Clin Exp Res 2007 Mar; 31(3):467-476
NIOSHTIC No.
20038278
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.
Keywords
Humans; Women; Age-groups; Alcoholic-beverages; Breast-cancer; Genetics; Cancer; Risk-factors; Metabolism; Author Keywords: Alcohol Dehydrogenase; Genotypes; Breast Cancer
Contact
Kala Visvanathan, MB, BS, FRACP, MHS, Department of Epidemiology, JohnsHopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205
CODEN
ACRSDM
Publication Date
20070301
Document Type
Journal Article
Email Address
kvisvana@jhsph.edu
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-OH-008428
Issue of Publication
3
ISSN
0145-6008
Source Name
Alcoholism: Clinical and Experimental Research
State
MD; NC
Performing Organization
Johns Hopkins University
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