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.