Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 785–792

Alcohol, genetics and risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial

  • Catherine A. McCarty
  • Douglas J. Reding
  • John Commins
  • Craig Williams
  • Meredith Yeager
  • James K. Burmester
  • Catherine Schairer
  • Regina G. Ziegler
Epidemiology

Abstract

We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55–74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.

Keywords

Breast cancer Alcohol Metabolizing enzyme Genetics Risk factors 

References

  1. 1.
    American Cancer Society (2010) Cancer facts and figures 2011. American Cancer Society, AtlantaGoogle Scholar
  2. 2.
    Singletary KW, Gapstur SM (2001) Alcohol and breast cancer. Review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286:2143–2151PubMedCrossRefGoogle Scholar
  3. 3.
    Ginsburg ES (1999) Estrogen, alcohol, and breast cancer risk. J Steroid Biochem Mol Biol 69:299–306PubMedCrossRefGoogle Scholar
  4. 4.
    Purohit V (2000) Can alcohol promote aromatization of androgens to estrogens? A review. Alcohol 20:123–127CrossRefGoogle Scholar
  5. 5.
    Wright RM, McManaman JL, Repine JE (1999) Alcohol-induced breast cancer: a proposed mechanism. Free Radic Biol Med 26:348–354PubMedCrossRefGoogle Scholar
  6. 6.
    Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS (eds) (2002) Goldfrank’s toxicologic emergencies, 7th edn. McGraw-Hill, New YorkGoogle Scholar
  7. 7.
    Stürmer T, Wang-Gohrke S, Arndt V, Boeing H, Kong Xkreienberg R et al (2002) Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer. Br J Cancer 87:519–523PubMedCrossRefGoogle Scholar
  8. 8.
    Freudenheim JL, Ambrosone CB, Moysich KB, Vena JE, Graham S, Marshall JR et al (1999) Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer. Cancer Cause Control 10:369–377CrossRefGoogle Scholar
  9. 9.
    Triano EA, Slusher LB, Atkins TA, Beneski JT, Gestl SA, Zolfaghari R et al (2003) Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer: implications for breast carcinogenesis. Cancer Res 63:3092–3100PubMedGoogle Scholar
  10. 10.
    Choi J-Y, Abel J, Neuhaus T, Ko Y, Harth V, Hamaima N et al (2003) Role of alcohol and genetic polymorphisms of CYP2E1 and ALDH2 in breast cancer development. Pharmacogenetics 13:67–72PubMedCrossRefGoogle Scholar
  11. 11.
    El-Rayes BF, Ali S, Heinbrun LK, Lababidi S, Bouwman D, Visscher D et al (2003) Cytochrome P450 and glutathione transferase expression in human breast cancer. Clin Cancer Res 9:1705–1709PubMedGoogle Scholar
  12. 12.
    Iscan M, Klaavuniemi T, Coban T, Kapucuoğlu N, Pelkonen O, Raunio H (2001) The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue. Breast Cancer Res Treat 70:47–54PubMedCrossRefGoogle Scholar
  13. 13.
    Kapucuoglu N, Coban T, Raunio H, Pelkonen O, Edwards RJ, Boobis AR, Iscan M (2003) Immunohistochemical demonstration of the expression of CYP2E1 in human breast tumour and non-tumour tissues. Cancer Lett 196:153–159PubMedCrossRefGoogle Scholar
  14. 14.
    Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford ED et al (2000) Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trial 21:273S–309SCrossRefGoogle Scholar
  15. 15.
    Thompson FE, Subar AF, Brown CC et al (2002) Cognitive research enhances accuracy of food frequency questionnaire reports: results of an experimental validation study. J Am Diet Assoc 102:212–225PubMedCrossRefGoogle Scholar
  16. 16.
    Subar AF, Ziegler RG, Thompson FE et al (2001) Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires. Am J Epidemiol 153:404–409PubMedCrossRefGoogle Scholar
  17. 17.
    Subar AF, Thompson FE, Smith AF et al (1995) Improving food frequency questionnaires: a qualitative approach using cognitive interviewing. J Am Diet Assoc 95:781–788PubMedCrossRefGoogle Scholar
  18. 18.
    Stolzenberg-Solomon RZ, Chang S-C, Leitzmann MF, Johnson KA, Johnson C, Buys SS et al (2006) Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 83:895–904PubMedGoogle Scholar
  19. 19.
    Visvanathan K, Crum RM, Strickland PT, You X, Ruczinski I, Berndt SI et al (2007) Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption and risk of breast cancer. Alcohol Clin Exp Res 31:467–476PubMedCrossRefGoogle Scholar
  20. 20.
    Hines LM, Hankinson SE, Smith-Warner SA, Spiegelman D, Kelsey KT, Colditz GA, Willett WC, Hunter DJ (2000) A prospective study of alcohol consumption and ADH3 genotype on plasma steroid hormone levels and breast cancer risk. Cancer Epidemiol Biomarker Prevent 9:1099–1105Google Scholar
  21. 21.
    Terry MB, Gammon MD, Zhang FF, Knight JA, Wang Q, Britton JA et al (2006) ADH3 genotype, alcohol intake and breast cancer risk. Carcinogenesis 27:840–847PubMedCrossRefGoogle Scholar
  22. 22.
    Fan S, Meng Q, Gao B, Grossman J, Yadegari M, Goldberg ID, Rosen EM (2000) Alcohol stimulates estrogen receptor signaling in human breast cancer cell lines. Cancer Res 60:5635–5639PubMedGoogle Scholar
  23. 23.
    Nasca PC, Liu S, Baptiste MS, Kwon CS, Jacobson H, Metzger BB (1994) Alcohol consumption and breast cancer: estrogen receptor status and histology. Am J Epidemiol 140:980–987PubMedGoogle Scholar
  24. 24.
    Enger SM, Paganini-Hill A, Longnecker MP, Bernstein L (1999) Alcohol consumption and breast cancer oestrogen and progesterone receptor status. Br J Cancer 79:1308–1314PubMedCrossRefGoogle Scholar
  25. 25.
    Li CI, Malone KE, Porter PL, Weiss NSC, Daling JR (2003) The relationship between alcohol use and risk of breast cancer by histology and hormone receptor status among women 65–79 years of age. Cancer Epidemiol Biomarker Prevent 12:1061–1066Google Scholar
  26. 26.
    Suzuki R, Ye W, Rylander-Rudqvist T, Saji S, Colditz GA, Wolk A (2005) Alcohol and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status: a prospective study. J Natl Cancer Inst 97:1601–1608PubMedCrossRefGoogle Scholar
  27. 27.
    Gapstur SM, Potter JD, Drinkard C, Folsom AR (1995) Synergistic effect between alcohol and estrogen replacement therapy on risk of breast cancer differs by estrogen/progesterone receptor status in the Iowa Women’s Health Study. Cancer Epidemiol Biomarker Prevent 4:313–318Google Scholar
  28. 28.
    Jasmine QL, Freedman ND, Leitzmann MF, Brinton LA, Hoover RN, Hollenbeck AR (2009) Alcohol and risk of breast cancer by histologic type and hormone receptor status in postmenopausal women. The NIH-AARP Diet and Health Study. Am J Epidemiol 170:308–317CrossRefGoogle Scholar
  29. 29.
    Crabb DW, Dipple KM, Thomasson HR (1993) Alcohol sensitivity, alcohol metabolism, risk of alcohol metabolism, and the role of alcohol and aldehyde dehydrogenase genotypes. J Lab Clin Med 122:234–240PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Catherine A. McCarty
    • 1
    • 2
  • Douglas J. Reding
    • 2
  • John Commins
    • 3
  • Craig Williams
    • 3
  • Meredith Yeager
    • 4
  • James K. Burmester
    • 2
  • Catherine Schairer
    • 4
  • Regina G. Ziegler
    • 4
  1. 1.Essentia Institute of Rural HealthDuluthUSA
  2. 2.Marshfield Clinic Research FoundationMarshfieldUSA
  3. 3.Information Management Services, Inc.RockvilleUSA
  4. 4.National Cancer InstituteBethesdaUSA

Personalised recommendations