Seungyoun Jung1, Molin Wang2, Kristin Anderson3, Laura Baglietto4, Leif Bergkvist5, Leslie Bernstein6, Piet A van den Brandt7, Louise Brinton8, Julie E Buring9, A Heather Eliassen10, Roni Falk8, Susan M Gapstur11, Graham G Giles4, Gary Goodman12, Judith Hoffman-Bolton13, Pamela L Horn-Ross14, Manami Inoue15, Laurence N Kolonel16, Vittorio Krogh17, Marie Lof18, Paige Maas8, Anthony B Miller19, Marian L Neuhouser12, Yikyung Park20, Kim Robien21, Thomas E Rohan22, Stephanie Scarmo23, Leo J Schouten7, Sabina Sieri17, Victoria L Stevens11, Schoichiro Tsugane24, Kala Visvanathan13, Lynne R Wilkens16, Alicja Wolk25, Elisabete Weiderpass26, Walter C Willett27, Anne Zeleniuch-Jacquotte23, Shumin M Zhang28, Xuehong Zhang29, Regina G Ziegler8, Stephanie A Smith-Warner30. 1. Department of Nutrition, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA, sjung@epi.umaryland.edu. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Division of Epidemiology and Community Health, School of Public Health, and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. 4. Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, VIC, Australia, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, VIC, Australia. 5. Department of Surgery and Centre for Clinical Research, Central Hospital, Västerås, Sweden. 6. Division of Cancer Etiology, Department of Population Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA. 7. Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 8. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, Bethesda, MD, USA. 9. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 11. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. 12. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 13. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 14. Cancer Prevention Institute of California, Fremont, CA, USA. 15. Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan, AXA Department of Health and Human Security, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. 16. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. 17. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 18. Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden. 19. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 20. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St Louis, St Louis, MO, USA. 21. Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA. 22. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. 23. Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA. 24. Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. 25. Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. 26. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway, Department of Research, Cancer Registry of Norway, Oslo, Norway and Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. 27. Department of Nutrition, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 28. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 29. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 30. Department of Nutrition, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. RESULTS: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. CONCLUSIONS: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
BACKGROUND:Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. RESULTS:Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. CONCLUSIONS:Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
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