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The CYP1A2 Genotype Modifies the Association Between Coffee Consumption and Breast Cancer Risk Among BRCA1 Mutation Carriers

¹ Centre for Research in Women's Health, Women's College Hospital, University of Toronto, Canada; ² Department of Nutritional Sciences, University of Toronto, Ontario, Canada; ³ Epidemiology Research Unit, Research Centre, Centre Hospitalier de l'Universitaire Montréal, CHUM Hôtel Dieu, Départment de Nutrition, Faculte du Medicine, Quebec, Canada; ⁴ Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Ohama, Nebraska; ⁵ Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania; ⁶ Departments of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; ⁷ Department of Gynecologic Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada; and ⁸ Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, California

Requests for reprints: Steven A. Narod, Centre for Research in Women's Health, 790 Bay Street, Room 750, Toronto, Ontario, Canada M5G 1N8. Phone: 416-351-3765; Fax: 416-351-3767. E-mail: steven.narod{at}wchospital.ca

We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations. (Cancer Epidemiol Biomarkers Prev 2007;16(5):912–6)

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				E. Bageman, C. Ingvar, C. Rose, and H. Jernstrom Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 895 - 901. [Abstract] [Full Text] [PDF]