title: The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers.
abstract: 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.
authors.affiliation: Centre for Research in Women's Health, Women's College Hospital, University of Toronto, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Carrie
authors.initials: C
authors.lastname: Snyder
authors.forename: Mary
authors.initials: M
authors.lastname: Daly
authors.forename: Susan
authors.initials: S
authors.lastname: Domchek
authors.forename: Susan
authors.initials: S
authors.lastname: Randall
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: Phil
authors.initials: P
authors.lastname: Zhang
authors.forename: Shiyu
authors.initials: S
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D002110:Caffeine / Q000008:administration & dosage* / Q000378:metabolism; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D003069:Coffee; D016001:Confidence Intervals; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019398:Genes, BRCA1; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
chemical_list: D003069:Coffee; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2