High coffee intake, but not caffeine, is associated with reduced estrogen receptor negative and postmenopausal breast cancer risk with no effect modification by CYP1A2 genotype.

Associations between caffeine and coffee consumption and breast cancer risk are uncertain, with studies suggesting inverse and null associations. Variation in cytochrome P450 1A2 (CYP1A2), a gene responsible for caffeine metabolism, may modify these associations. Cases (n = 3,062) were recruited through the Ontario Cancer Registry and controls (n = 3,427) through random digit dialing. Logistic regression was used to evaluate associations between breast cancer risk and intakes of 7 caffeine-containing items and total caffeine, and examine whether a genetic variant in CYP1A2 (rs762551) modified these associations. Analyses were stratified by estrogen receptor (ER), menopausal, and smoking status. Generally, coffee and caffeine were not associated with breast cancer risk; however, a significant reduction in risk was observed with the highest category of coffee consumption [≥5 cups per day vs. never, multivariate-adjusted odds ratio (MVOR) = 0.71, 95% confidence interval (CI): 0.51, 0.98]. Variant rs762551 did not modify associations. In stratified analyses, high coffee intake was associated with reduced risk of ER- (MVOR = 0.41, 95% CI: 0.19, 0.92) and postmenopausal breast cancer (MVOR = 0.63, 95% CI: 0.43, 0.94). High coffee consumption, but not total caffeine, may be associated with reduced risk of ER- and postmenopausal breast cancers, independent of CYP1A2 genotype. Further studies are needed to replicate these findings.