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J Natl Cancer Inst. 2014 Dec 12;107(1):367. doi: 10.1093/jnci/dju367. Print 2015 Jan.

Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition.

Author information

International Agency for Research on Cancer (IARC), Lyon, France (JdB, PF, VC, JYP, NS, FM, IR); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (KO); Danish Cancer Society Research Center, Copenhagen, Denmark (NR, AT); Inserm, Centre for research in Epidemiology and Population Health (CESP), Villejuif, France (MCBR, FCC, GF); Université Paris Sud, Villejuif, France (MCBR, FCC, GF); Institute Gustave Roussy, Villejuif, France (MCBR, FCC, GF); Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (VK, RK); Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany (MMB); Hellenic Health Foundation, Athens, Greece (AT, DT); Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece (PL); Department of Epidemiology, Harvard School of Public Health, Boston, MA (PL, DT); Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece (PL, DT); Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy (DP); Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (SSi); Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy (SP); Cancer Registry and Histopathology Unit, "Civic - M.P.Arezzo" Hospital, Ragusa, Italy (RT); Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (PV, HBBdM, PHP, ER); HuGeF Foundation, Torino, Italy (PV); National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands (HBBdM); Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands (HBBdM); Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands (PHP); Department of Nutrition, Institute of Basic Medical



There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).


A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided.


A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035).


Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

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