Skip to main content

Advertisement

SpringerLink
Log in

Alcohol and folate intake and breast cancer risk in the WHI Observational Study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship. Objective To examine the relationship among breast cancer, alcohol and folate in the Women’s Health Initiative-Observational Study (WHI-OS). Methods 88,530 postmenopausal women 50–79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer. Results 1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001–1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96–1.32; >5–15 g/d HR = 1.14, 95%CI 0.99–1.31; and >15 g/d HR = 1.13 95%CI 0.96–1.32). We found no significant interaction between alcohol and folate in our adjusted model. Conclusions We found no evidence for folate attenuating alcohol’s effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Williams RR, Horm JW (1977) Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 58:525–547

    PubMed  CAS  Google Scholar 

  2. van den Brandt PA, Goldbohm RA, Van’t Veer P (1995) Alcohol and breast cancer: results from The Netherlands Cohort Study. Am J Epidemiol 141:907–915

    PubMed  Google Scholar 

  3. Rohan TE, Jain M, Howe GR, Miller AB (2000) Alcohol consumption and risk of breast cancer: a cohort study. Cancer Causes Control 11:239–247

    Article  PubMed  CAS  Google Scholar 

  4. Schatzkin A, Jones DY, Hoover RN, Taylor PR, Brinton LA, Ziegler RG, Harvey EB, Carter CL, Licitra LM, Dufour MC et al (1987) Alcohol consumption and breast cancer in the epidemiologic follow-up study of the first National Health and Nutrition Examination Survey. N Engl J Med 316:1169–1173

    PubMed  CAS  Google Scholar 

  5. Friedenreich CM, Howe GR, Miller AB, Jain MG (1993) A cohort study of alcohol consumption and risk of breast cancer. Am J Epidemiol 137:512–520

    PubMed  CAS  Google Scholar 

  6. Longnecker MP, Berlin JA, Orza MJ, Chalmers TC (1988) A meta-analysis of alcohol consumption in relation to risk of breast cancer. JAMA 260:652–656

    Article  PubMed  CAS  Google Scholar 

  7. Longnecker MP (1994) Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes Control 5:73–82

    Article  PubMed  CAS  Google Scholar 

  8. Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR et al (1998) Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279:535–540

    Article  PubMed  CAS  Google Scholar 

  9. Baglietto L, English DR, Gertig DM, Hopper JL, Giles GG (2005) Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. BMJ 331:807

    Article  PubMed  CAS  Google Scholar 

  10. Rohan TE, Jain MG, Howe GR, Miller AB (2000) Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 92:266–269

    Article  PubMed  CAS  Google Scholar 

  11. Sellers TA, Kushi LH, Cerhan JR, Vierkant RA, Gapstur SM, Vachon CM, Olson JE, Therneau TM, Folsom AR (2001) Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 12:420–428

    Article  PubMed  CAS  Google Scholar 

  12. Zhang S, Hunter DJ, Hankinson SE, Giovannucci EL, Rosner BA, Colditz GA, Speizer FE, Willett WC (1999) A prospective study of folate intake and the risk of breast cancer. JAMA 281:1632–1637

    Article  PubMed  CAS  Google Scholar 

  13. Zhang SM, Willett WC, Selhub J, Hunter DJ, Giovannucci EL, Holmes MD, Colditz GA, Hankinson SE (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 95:373–380

    Article  PubMed  CAS  Google Scholar 

  14. Feigelson HS, Jonas CR, Robertson AS, McCullough ML, Thun MJ, Calle EE (2003) Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 12:161–164

    PubMed  CAS  Google Scholar 

  15. Rosenberg IH (1999) Virtual folate: virtual success? Am J Clin Nutr 70:177–178

    PubMed  CAS  Google Scholar 

  16. Costello JF, Plass C (2001) Methylation matters. J Med Genet 38:285–303

    Article  PubMed  CAS  Google Scholar 

  17. Homann N, Tillonen J, Salaspuro M (2000) Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency. Int J Cancer 86:169–173

    Article  PubMed  CAS  Google Scholar 

  18. Singletary KW, Gapstur SM (2001) Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286:2143–2151

    Article  PubMed  CAS  Google Scholar 

  19. Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55:578–592

    Article  PubMed  CAS  Google Scholar 

  20. Choi S, Mason J (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132

    PubMed  CAS  Google Scholar 

  21. Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88

    Article  PubMed  CAS  Google Scholar 

  22. Anderson G, Cummings S, Freedman LS, et al. (1998) Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials 19:61–109

    Google Scholar 

  23. WHI (2003) Women’s Health Initiative Semi-Annual Progress Report: March 1 2002 to August 31 2002

  24. Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9:178–187

    Article  PubMed  CAS  Google Scholar 

  25. Commenges D, Letenneur L, Joly P (1997) Re: “Serum transferrin saturation, stroke incidence, and mortality in women and men. The NHANES I Epidemiologic Followup Study”. Am J Epidemiol 146:683–684

    PubMed  CAS  Google Scholar 

  26. Korn EL, Graubard BI, Midthune D (1997) Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol 145:72–80

    PubMed  CAS  Google Scholar 

  27. Thiebaut AC, Benichou J (2004) Choice of time-scale in Cox’s model analysis of epidemiologic cohort data: a simulation study. Stat Med 23:3803–3820

    Article  PubMed  Google Scholar 

  28. Chang SC, Ziegler RG, Dunn B, Stolzenberg-Solomon R, Lacey JV Jr, Huang WY, Schatzkin A, Reding D, Hoover RN, Hartge P et al (2006) Association of energy intake and energy balance with postmenopausal breast cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 15:334–341

    Article  PubMed  Google Scholar 

  29. Doody MM, Freedman DM, Alexander BH, Hauptmann M, Miller JS, Rao RS, Mabuchi K, Ron E, Sigurdson AJ, Linet MS (2006) Breast cancer incidence in U.S. radiologic technologists. Cancer 106:2707–2715

    Article  PubMed  Google Scholar 

  30. Harvie M, Howell A, Vierkant RA, Kumar N, Cerhan JR, Kelemen LE, Folsom AR, Sellers TA (2005) Association of gain and loss of weight before and after menopause with risk of postmenopausal breast cancer in the Iowa women’s health study. Cancer Epidemiol Biomarkers Prev 14:656–661

    Article  PubMed  Google Scholar 

  31. Radimer KL, Ballard-Barbash R, Miller JS, Fay MP, Schatzkin A, Troiano R, Kreger BE, Splansky GL (2004) Weight change and the risk of late-onset breast cancer in the original Framingham cohort. Nutr Cancer 49:7–13

    Article  PubMed  Google Scholar 

  32. Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Wolk A (2006) Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: a prospective cohort study. Int J Cancer 119:1683–1689

    Article  PubMed  CAS  Google Scholar 

  33. Tehard B, Lahmann PH, Riboli E, Clavel-Chapelon F (2004) Anthropometry, breast cancer and menopausal status: use of repeated measurements over 10 years of follow-up-results of the French E3 N women’s cohort study. Int J Cancer 111:264–269

    Article  PubMed  CAS  Google Scholar 

  34. Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27

    PubMed  CAS  Google Scholar 

  35. Therneau TM (2000) Grambsch PM: modeling survival data: extending the Cox Model, 1st edn. Springer, New York

    Google Scholar 

  36. Ellison RC, Zhang Y, McLennan CE, Rothman KJ (2001) Exploring the relation of alcohol consumption to risk of breast cancer. Am J Epidemiol 154:740–747

    Article  PubMed  CAS  Google Scholar 

  37. Sellers TA, Vierkant RA, Cerhan JR, Gapstur SM, Vachon CM, Olson JE, Pankratz VS, Kushi LH, Folsom AR (2002) Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Cancer Epidemiol Biomarkers Prev 11:1104–1107

    PubMed  CAS  Google Scholar 

  38. Zhang SM, Lee IM, Manson JE, Cook NR, Willett WC, Buring JE (2007) Alcohol consumption and breast cancer risk in the Women’s Health Study. Am J Epidemiol 165:667–676

    Article  PubMed  Google Scholar 

  39. Tjonneland A, Christensen J, Olsen A, Stripp C, Nissen SB, Overvad K, Thomsen BL (2006) Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark. Eur J Clin Nutr 60:280–286

    Article  PubMed  CAS  Google Scholar 

  40. Ubbink J (1998) Should all elderly people receive folate supplements? Drugs Aging 16:415–420

    Article  Google Scholar 

  41. Lewis CJ, Crane NT, Wilson DB, Yetley EA (1999) Estimated folate intakes: data updated to reflect food fortification, increased bioavailability, and dietary supplement use. Am J Clin Nutr 70:198–207

    PubMed  CAS  Google Scholar 

  42. Giovannucci E, Stampfer MJ, Colditz GA, Manson JE, Rosner BA, Longnecker MP, Speizer FE, Willett WC (1993) Recall and selection bias in reporting past alcohol consumption among breast cancer cases. Cancer Causes Control 4:441–448

    Article  PubMed  CAS  Google Scholar 

  43. Feunekes GI, Van’t Veer P, van Staveren WA, Kok FJ (1999) Alcohol intake assessment: the sober facts. Am J Epidemiol 150:105–112

    PubMed  CAS  Google Scholar 

  44. Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF, Johnson KA, Johnson C, Buys SS, Hoover RN, Ziegler RG (2006) Folate intake, alcohol use, and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Clin Nutr 83:895–904

    PubMed  CAS  Google Scholar 

  45. Munger RG, Folsom AR, Kushi LH, Kaye SA, Sellers TA (1992) Dietary assessment of older Iowa women with a food frequency questionnaire: nutrient intake, reproducibility, and comparison with 24-hour dietary recall interviews. Am J Epidemiol 136:192–200

    PubMed  CAS  Google Scholar 

  46. Flagg EW, Coates RJ, Calle EE, Potischman N, Thun MJ (2000) Validation of the American Cancer Society Cancer Prevention Study II Nutrition Survey Cohort Food Frequency Questionnaire. Epidemiology 11:462–468

    Article  PubMed  CAS  Google Scholar 

  47. Administration FaD (1996) Food standards: amendment of standards of identity for enriched grain products to require the addition of folic acid, final rule. Fed Regist 61:8781–8797

    Google Scholar 

  48. Bentley TG, Willett WC, Weinstein MC, Kuntz KM (2006) Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification. Am J Public Health 96:2040–2047

    Article  PubMed  Google Scholar 

  49. Thygesen LC, Morch LS, Keiding N, Johansen C, Gronbaek M (2008) Use of baseline and updated information on alcohol intake on risk for breast cancer: importance of latency. Int J Epidemiol 37:669–677

    Google Scholar 

  50. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC (1998) Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 129:517–524

    PubMed  CAS  Google Scholar 

  51. Helping patients with alcohol problems (http://www.niaaa.nih.gov/publications/Practitioner/HelpingPatients.html)

Download references

Acknowledgements

This work was funded by NHLBI grant #1RO3CA99491-01.

Author information

Authors and Affiliations

  1. Division of General Internal Medicine, Rhode Island Hospital, Brown University Medical School, 111 Plain Street, Providence, RI, 02903, USA

    Christine M. Duffy

  2. Global Epidemiology and Risk Management Pfizer, Inc., New London, CT, USA

    Annlouise Assaf

  3. Division of General Internal Medicine, Brown University Medical School, Providence, RI, USA

    Michele Cyr

  4. College of Health & Sciences, Walden University, Minneapolis, MN, USA

    Gary Burkholder

  5. Memorial Hospital of Pawtucket, Pawtucket, RI, USA

    Elizabeth Coccio

  6. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA

    Tom Rohan

  7. Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA

    Anne McTiernan

  8. Division of Epidemiology, Ohio State University, Columbus, OH, USA

    Electra Paskett

  9. Department of Preventive Medicine, Stony Brook University Medical School, Stony Brook, NY, USA

    Dorothy Lane

  10. Department of Family Medicine, Boston University Medical School, Boston, MA, USA

    V. K. Chetty

Authors
  1. Christine M. Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annlouise Assaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele Cyr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary Burkholder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elizabeth Coccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tom Rohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anne McTiernan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Electra Paskett
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dorothy Lane
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. V. K. Chetty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christine M. Duffy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duffy, C.M., Assaf, A., Cyr, M. et al. Alcohol and folate intake and breast cancer risk in the WHI Observational Study. Breast Cancer Res Treat 116, 551–562 (2009). https://doi.org/10.1007/s10549-008-0167-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0167-2

Keywords

Search

Navigation