Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer.
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.
Visvanathan
Kala
K
Department of Epidemiology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. kvisvana@jhsph.edu
Crum
Rosa M
RM
Strickland
Paul T
PT
You
Xiaojun
X
Ruczinski
Ingo
I
Berndt
Sonja I
SI
Alberg
Anthony J
AJ
Hoffman
Sandra C
SC
Comstock
George W
GW
Bell
Douglas A
DA
Helzlsouer
Kathy J
KJ
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
D000426:Alcohol Dehydrogenase