Cancer Causes & Control

, Volume 10, Issue 5, pp 369-377

First online:

Alcohol dehydrogenase 3 genotype modification of the associationof alcohol consumption with breast cancer risk

  • Jo L. FreudenheimAffiliated withDepartment of Social and Preventive Medicine
  • , Christine B. AmbrosoneAffiliated withDivision of Molecular Epidemiology, National Center for Toxicological Research
  • , Kirsten B. MoysichAffiliated withRoswell Park Cancer Institute, Cancer Epidemiology and Prevention
  • , John E. VenaAffiliated withDepartment of Social and Preventive Medicine
  • , Saxon GrahamAffiliated withDepartment of Social and Preventive Medicine
  • , James R. MarshallAffiliated withArizona Cancer Center
  • , Paola MutiAffiliated withDepartment of Social and Preventive Medicine
  • , Rosemary LaughlinAffiliated withDepartment of Social and Preventive Medicine
  • , Takuma NemotoAffiliated withDepartment of Surgery, State University of New York
    • , Lea C. HartyAffiliated withDivision of Cancer Epidemiology and Genetics
    • , G. Adam CritsAffiliated withLaboratory of Human Carcinogenesis, National Cancer Institute
    • , Arthur W.K. ChanAffiliated withResearch Institute on Addictions
    • , Peter G. ShieldsAffiliated withLaboratory of Human Carcinogenesis, National Cancer Institute

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Objectives: Because alcohol dehydrogenase 3 (ADH3) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH3 genotype in relation to alcohol intake and breast cancer risk.

Methods: We conducted a case–control study among Caucasian women aged 40–85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression.

Results: We found increased risk among pre- (OR 2.3, 95%, CI 1.2–4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7–1.7) associated with ADH3 1-1 compared to ADH3 1-2 and ADH3 2-2 genotypes. Risk was increased for premenopausal women with the ADH3 1-1 genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5–8.8) compared to lighter drinkers with the ADH3 2-2 or ADH3 1-2 genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption.

Conclusion: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk.

alcohol alcohol dehydrogenase breast neoplasms epidemiology genetic polymorphisms