Cancer Causes & Control

, Volume 17, Issue 9, pp 1209–1213 | Cite as

Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women

  • Martin Lajous
  • Isabelle Romieu
  • Severine Sabia
  • Marie-Christine Boutron-Ruault
  • Françoise Clavel-ChapelonEmail author
Brief Report



Adequate folate intake may be important for breast cancer prevention. Its protective effect may be influenced by factors associated with folate metabolism. We sought to evaluate folate intake in relation to breast cancer risk and examine whether the relation is affected by alcohol and intake of vitamin B2 and B12.


A prospective cohort analysis of folate intake was conducted among 62,739 postmenopausal women in the French E3N cohort who had completed a validated food frequency questionnaire in 1993. During nine years’ follow-up, 1,812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized in quintiles and energy-adjusted using the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known breast cancer determinants.


The multivariate RR for extreme quintiles of folate intake was 0.78 (95% CI: 0.67–0.90; p-trend = 0.001) [Median intake for Q1 = 296 μg/day and Q5 = 522 μg/day]. There was no evidence to support effect modification by alcohol or B2 intake. The decreasing trend was most marked in women with higher folate and vitamin B12 intake. However, test for interaction was not statistically significant (p = 0.29).


High folate intake was associated with decreased breast cancer risk. Vitamin B12 intake may modify this association.


Breast cancer Women Nutrition Folate Vitamin B12 Vitamin B2 Alcohol Diet 



The E3N team is indebted to all participants for providing the data used in this study, to their physicians for providing pathology reports, and to G. Evans for the linguistic revision of the manuscript. We thank the French League against Cancer, the European Community, the 3M Company, the Mutuelle Générale de l’Education Nationale, the Institut Gustave Roussy and the Institut National de la Santé et de la Recherche Médicale for their financial support of the E3N study.


  1. 1.
    Mason JB, Choi SW (2000) Folate and carcinogenesis: developing a unifying hypothesis. Advan Enzyme Regul 40:127–141CrossRefGoogle Scholar
  2. 2.
    Duthie SJ, Narayanan S, Blum S, Pirie L, Brand GM (2000) Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells. Nutr Cancer 37:245–251PubMedCrossRefGoogle Scholar
  3. 3.
    Szyf M, Pakneshan P, Rabanni SA (2004) DNA methylation and breast cancer. Biochem Pharm 68:1187–1197PubMedCrossRefGoogle Scholar
  4. 4.
    Mason JB, Choi SW (2005) Effects of alcohol on folate metabolism: implications for carcinogenesis. Alcohol 35:235–241PubMedCrossRefGoogle Scholar
  5. 5.
    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 Biomark Prev 12:161–164Google Scholar
  6. 6.
    Zhang S, Hunter DJ, Hankinson SE, et al (1999) A prospective study of folate intake and the risk of breast cancer. JAMA 281:1632–1637PubMedCrossRefGoogle Scholar
  7. 7.
    Rohan TE, Jain MG, Howe GR, Miller AB (2000) Dietary folate consumption and breast cancer risk. JNCI 92:266–269PubMedCrossRefGoogle Scholar
  8. 8.
    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. Epidemiology 12:420–428PubMedCrossRefGoogle Scholar
  9. 9.
    Biglietto L, English DR, Gertig DM, Hopper JL, Giles GL (2005) Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. BMJ 331:807–810CrossRefGoogle Scholar
  10. 10.
    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 61:7136–7141PubMedGoogle Scholar
  11. 11.
    Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I (2006) Folate, vitamin B6 and vitamin B12 intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomark Prev 15:443–448CrossRefGoogle Scholar
  12. 12.
    Touvier M, Kesse E, Clavel-Chapelon F, Boutron-Ruault MC (2005) Dual association of beta-carotene with risk of tobacco-related cancers in a cohort of French women. J Natl Cancer Inst 97:1338–1344PubMedCrossRefGoogle Scholar
  13. 13.
    Schofield WN (1985) Predicting basal metabolic rate, new standards, review of previous work. Hum Nutr Clin Nutr 39C:5–41Google Scholar
  14. 14.
    van Liere MJ, Lucas F, Clavel F, Slimani N, Villeminot S (1997) Relative validity and reproducibility of a French dietary history questionnaire. Int J Epidemiol 26(Suppl 1):S128–S136PubMedCrossRefGoogle Scholar
  15. 15.
    Favier JC, Ireland-Ripert J, Toque C, Feinberg M (1995) Répertoire Général des Aliments. Table de composition (Composition tables). INRA, CIQUAL-REGAL, Tec & Doc Lavoisier, ParisGoogle Scholar
  16. 16.
    Gaudet MM, Britton JA, Kabat GC, et al (2004) Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status. Cancer Epidemiol Biomark Prev 13:1485–1494Google Scholar
  17. 17.
    Willett W, Stampfer M (1998) Implications of total energy intake for epidemiologic analysis. In: Willett W (ed) Nutritional epidemiology, 2nd edn. Oxford University Press, New York, pp 273–301Google Scholar
  18. 18.
    Cho E, Spiegelman D, Hunter DJ, et al (2003) Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer. Cancer Epidemiol Biomark Prev 12:713–720Google Scholar
  19. 19.
    Zhang S, Willet WC, Selhub J, et al (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine and risk of breast cancer. JNCI 95:373–380PubMedGoogle Scholar
  20. 20.
    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(2):152–158PubMedCrossRefGoogle Scholar
  21. 21.
    Fowler BM, Giuliano AR, Piyathilake C, Nour M, Hatch K (1998) Hypomethylation in cervical tissue: is there a correlation with folate status? Cancer Epidemiol Biomark Prev 7:901–906Google Scholar
  22. 22.
    Jacob RA, Gretz DM, Taylor PC, et al (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128:1204–1212PubMedGoogle Scholar
  23. 23.
    Fenech M, Baghurst P, Luderer W, et al (2005) Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability – results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 26:991–999PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Martin Lajous
    • 1
    • 2
  • Isabelle Romieu
    • 2
  • Severine Sabia
    • 1
  • Marie-Christine Boutron-Ruault
    • 1
  • Françoise Clavel-Chapelon
    • 1
    Email author
  1. 1.Inserm, (Institut National de la Santé et de la Recherche Médicale), ERI 20Institut Gustave RoussyVillejuif CedexFrance
  2. 2.Center for Population Health ResearchInstituto Nacional de Salud PublicaCuernavacaMexico

Personalised recommendations