Cancer Causes & Control

, Volume 15, Issue 10, pp 1085–1093 | Cite as

Association of folate and alcohol with risk of ovarian cancer in a prospective study of postmenopausal women

  • Linda E. Kelemen
  • Thomas A. Sellers
  • Robert A. Vierkant
  • Lisa Harnack
  • James R. Cerhan
Article

Abstract

Studies evaluating the association of ovarian cancer with alcohol intake are inconsistent, and few have evaluated this association in the context of folate consumption. Dietary folate and alcohol intakes and lifestyle and medical information were collected with self-administered questionnaires in 1986 from postmenopausal women aged 55–69 followed prospectively for 15 years for risk of epithelial ovarian cancer in the Iowa Women's Health Study. Among 27,205 eligible women free of baseline cancer, 147 incident epithelial ovarian cancer cases were identified by linkage to a cancer registry. Compared to the lowest quartile of total folate (food plus supplement) intake, the multivariable risk ratios (RR) for increasing quartiles were 1.0 (referent), 1.59, 1.24, 1.73 (95% confidence interval [CI], 0.90–3.33; p for trend, 0.20). Compared to non-drinkers, the RRs for increasing alcohol intake were 1.0 (referent), 0.78 for 0.01–3.9 g/d, 0.75 for 4.0–9.9 g/d and 0.58 for ≥10 g/d (95% CI, 0.30–1.11; p for trend, 0.08). Among women with alcohol intake ≥4 g/d compared to <4 g/d, the apparent risk reduction was limited to those with total folate intake ≥331 μg/d (RR, 0.52; 95% CI, 0.22–1.19; p for interaction, 0.04) although this estimate was based on only seven cases. The association did not change appreciably when we excluded tumors of mucinous histology. These findings suggest that alcohol consumption is inversely related to postmenopausal ovarian cancer, and that the association of folate with ovarian cancer may vary by the amount of alcohol consumed.

ethanol folic acid ovarian neoplasms prospective studies women 

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References

  1. 1.
    American Cancer Society (2003) Cancer Facts and Figures, 2003. Atlanta, GA: ACS. www.cancer.org/docroot/stt/tt_0.asp. Ac-cessed August 20, 2003.Google Scholar
  2. 2.
    Holschneider CH, Berek JS (2000) Ovarian cancer:epidemiology, biology, and prognostic factors.Semin Surg Oncol 19: 3–10.Google Scholar
  3. 3.
    Kushi LH, Mink PJ, Folsom AR, et al.(1999) Prospective study of diet and ovarian cancer.Am J Epidemiol 149: 21–31.Google Scholar
  4. 4.
    Shrubsole MJ, Jin F, Dai Q, et al.(2001) Dietary folate intake and breast cancer risk:results from the Shanghai Breast Cancer Study. Cancer Res 61&: 7136–71Google Scholar
  5. 5.
    Zhang SM, Willett WC, Selhub J, et al.(2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 95&: 373–3Google Scholar
  6. 6.
    Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G (1991) Folate intake and carcinogen-esis of the colon and rectum.Int J Epidemiol 20: 368–374.Google Scholar
  7. 7.
    Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Willett WC (1995) Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men.J Natl Cancer Inst 87: 265–273.Google Scholar
  8. 8.
    Giovannucci E, Stampfer MJ, Colditz GA, et al.(1998) Multi-vitamin use, folate, and colon cancer in women in the Nurses' Health Study.Ann Int Med 129: 517–524.Google Scholar
  9. 9.
    Glynn SA, Albanes D, Pietinen P, et al.(1996) Colorectal cancer and folate status:a nested case–control study among male smokers.Cancer Epidemiol Biomarkers Prev 5: 487–494.Google Scholar
  10. 10.
    Su LJ, Arab L (2001) Nutritional status of folate and colon cancer risk:evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 11&: 65–Google Scholar
  11. 11.
    Smith-Warner SA, Spiegelman D, Yaun SS, et al.(1998) Alcohol and breast cancer in women:a pooled analysis of cohort studies. J Am Med Assoc 279&: 535–5Google Scholar
  12. 12.
    Giovannucci E (2002) Epidemiologic studies of folate and colorectal neoplasia:a review.J Nutr 132: 2350S–2355S.Google Scholar
  13. 13.
    Blount BC, Mack MM, Wehr CM, et al.(1997) Folate de ciency causes uracil misincorporation into human DNA and chromosome breakage:implications for cancer and neuronal damage.Proc Natl Acad Sci USA 94: 3290–3295.Google Scholar
  14. 14.
    Stern LL, Mason JB, Selhub J, Choi SW (2000) Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene.Cancer Epidemiol Biomarkers Prev 9: 849–853.Google Scholar
  15. 15.
    Strathdee G, Appleton K, Illand M, et al.(2001) Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes.Am J Pathol 158: 1121–1127.Google Scholar
  16. 16.
    Herman JG (2002) Hypermethylation pathways to colorectal cancer.Implications for prevention and detection.Gastroenterol Clin North Am 31: 945–958.Google Scholar
  17. 17.
    Hillman RS, Steinberg SE (1982) The effects of alcohol on folate metabolism.Ann Rev Med 33: 345–354.Google Scholar
  18. 18.
    Kato I, Tominaga S, Terao C (1989) Alcohol consumption and cancers of hormone-related organs in females.Jpn J Clin Oncol 19: 202–207.Google Scholar
  19. 19.
    Goodman MT, Tung KH (2003) Alcohol consumption and the risk of borderline and invasive ovarian cancer.Obstet Gynecol 101: 1221–1228.Google Scholar
  20. 20.
    Whittemore AS, Wu ML, Paffenbarger RS Jr, et al.(1988) Personal and environmental characteristics related to epithelial ovarian cancer.II.Exposures to talcum powder, tobacco, alcohol, and coffee.Am J Epidemiol 128: 1228–1240.Google Scholar
  21. 21.
    Gwinn ML, Webster LA, Lee NC, Layde PM, Rumbin GL, and the Cancer and Steroid Hormone Study Group (1986) Alcohol consumption and ovarian cancer risk.Am J Epidemiol 123: 759–766.Google Scholar
  22. 22.
    Kuper H, Titus-Ernstoff L, Harlow BL, Cramer DW (2000) Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer.Int J Cancer 88: 313–318.Google Scholar
  23. 23.
    Nandakumar A, Anantha N, Dhar M, et al.(1995) A case–control investigation on cancer of the ovary in Bangalore, India.Int J Cancer 63: 361–365.Google Scholar
  24. 24.
    Salazar-Martinez E, Lazcano-Pone EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Hernandez-Avila M (2002) Nutritional determinants of epithelial ovarian cancer risk:a case–control study in Mexico.Oncology 63: 151–157.Google Scholar
  25. 25.
    McCann SE, Freudenheim JL, Marshall JR, Graham S (2003) Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups.J Nutr 133: 1937–1942.Google Scholar
  26. 26.
    Bidoli E, Lavecchia C, Talamini R, et al.(2001) Micronutrients and ovarian cancer:a case–control study in Italy.Ann Oncology 12: 1589–1593.Google Scholar
  27. 27.
    Larsson SC, Giovannucci E, Wolk A (2004) Dietary folate intake and incidence of ovarian cancer:The Swedish Mammography Cohort.J Nat Cancer Inst 96: 396–402.Google Scholar
  28. 28.
    Bisgard KM, Folsom AR, Hong CP, Sellers TA (1994) Mortality and cancer rates in non-respondents to a prospective study of older women:5-year follow-up.Am J Epidemiol 139: 990–1000.Google Scholar
  29. 29.
    Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals.Am J Epidemiol 135: 1114–1126.Google Scholar
  30. 30.
    Gapstur SM, Potter JD, Sellers TA, Kushi LH, Folsom AR (1993) Alcohol consumption and postmenopausal endometrial cancer: results from the Iowa Women 's Health Study.Cancer Causes Control 4: 323–329.Google Scholar
  31. 31.
    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.Google Scholar
  32. 32.
    United States Department of Health and Human Services, United States Public Health Service (1984) SEER Program:Cancer Incidence and Mortality in the United States. Bethesda, MD: National Cancer Institute, pp.1073–1081.Google Scholar
  33. 33.
    Serov SF, Scully RE, Sobin LH (1973) International Histological Classi cation of Tumors.No.9.Histological Typing of Ovarian Tumors. Geneva, Switzerland: World Health Organization.Google Scholar
  34. 34.
    Willett WC, Stampfer MJ (1986) Total energy intake:implications for epidemiologic analyses.Am J Epidemiol 124: 17–27.Google Scholar
  35. 35.
    Therneau TM, Grambsch PM (2000) Modeling Survival Data: Extending the Cox Model. New York, NY: Springer-Verlag, pp.87–126.Google Scholar
  36. 36.
    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.Google Scholar
  37. 37.
    Modugno F, Ness RB, Allen GO (2003) Alcohol consumption and the risk of mucinous and nonmucinous epithelial ovarian cancer. Obstet Gynecol 102&: 1336–13Google Scholar
  38. 38.
    Steinberg SE, Campbell CL, Hillman RS (1982) Effect of alcohol on tumor folate supply.Biochem Pharmacol 31: 1461–1463.Google Scholar
  39. 39.
    Kim Y-I (2003) Role of folate in colon cancer development and progression.J Nutr 133: 3731S–3739S.Google Scholar
  40. 40.
    Webb PM, Purdie DM, Bain CJ, Green AC (2004).Alcohol, wine, and risk of epithelial ovarian cancer.Cancer Epidemiol Biomarkers Prev 13: 592–599.Google Scholar
  41. 41.
    Schouten LJ, Zeegers MPA, Goldbohm A, van den Brandt PA (2004).Alcohol and ovarian cancer risk:results from the Netherlands Cohort Study.Cancer Causes Control 15: 201–209.Google Scholar
  42. 42.
    La Vecchia C, Negri E, Franceschi S, Parazzini F, Gentile A, Fasoli M (1992).Alcohol and epithelial ovarian cancer.J Clin Epidemiol 45: 1025–1030.Google Scholar
  43. 43.
    Tavani A, Gallus S, Dal Maso L, Franceschi S, Montella M, Conti E, La Vecchia C (2001).Coffee and alcohol intake and risk of ovarian cancer:an Italian case-control study.Nutr Cancer 39: 29–34.Google Scholar
  44. 44.
    Zhang SM, Hunter DJ, Rosner BA, et al.(2000) Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin 's lymphoma among women.Cancer Epidemiol Biomarkers Prev 9: 477–485.Google Scholar
  45. 45.
    Sellers TA, Kushi LH, Cerhan JR, et al.(2001) Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.Epidemiol 12: 420–428.Google Scholar
  46. 46.
    Harnack L, Jacobs DR Jr, Nicodemus K, Lazovich D, Anderson K, Folsom AR (2002) Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutr Cancer 43&: 152–1Google Scholar
  47. 47.
    Rohan TE, Jain MG, Howe GR, Miller AB (2000) Dietary folate consumption and breast cancer risk.J Natl Cancer Inst 92: 266–269.Google Scholar
  48. 48.
    Zhang S, Hunter DJ, Hankinson SE, et al.(1999) A prospective study of folate intake and the risk of breast cancer.J Am Med Assoc 281: 1632–1637.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Linda E. Kelemen
    • 1
  • Thomas A. Sellers
    • 2
  • Robert A. Vierkant
    • 1
  • Lisa Harnack
    • 3
  • James R. Cerhan
    • 1
  1. 1.Department of Health Sciences ResearchMayo Clinic College of MedicineRochesterUSA
  2. 2.H. Lee Moffitt Cancer Center & Research InstituteTampaUSA
  3. 3.Division of Epidemiology, School of Public HealthUniversity of MinnesotaMinneapolisUSA

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