Lifestyle and genetic risk factors for postmenopausal breast cancer in the multiethnic cohort

Abstract Background Adherence to a healthy lifestyle has been consistently associated with reduced breast cancer risk, but whether this benefit varies by genetic susceptibility remains unclear, particularly among racially and ethnically diverse populations. Methods In this prospective cohort analysis, we evaluated the association between a healthy lifestyle index score (HLIS), constructed from diet, alcohol consumption, body mass index, waist circumference, physical activity, and smoking, and risk of invasive breast cancer among postmenopausal women. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) among 22,725 postmenopausal women in the Multiethnic Cohort (MEC), self-identified as White (22%), African American (13%), Native Hawaiian (8%), Japanese American (38%), and Latino (19%). We also evaluated effect modification by a 313-variant polygenic risk score (PRS) for breast cancer. Results Higher HLIS was associated with a decreased risk of postmenopausal breast cancer. Compared with women in the low HLIS, those in the high HLIS had a 33% lower risk of breast cancer (HR = 0.67; 95% CI: 0.57 to 0.79). Results were similar across the two PRS strata, and we did not observe a multiplicative interaction between HLIS and PRS (low-PRS group: HR = 0.63, 95% CI: 0.48 to 0.82; high-PRS group: HR = 0.70; 95% CI: 0.57 to 0.85; P-interaction=0.48). In race/ethnicity-stratified analyses, the inverse associations were most evident among White and Japanese American women. Conclusion In this multiethnic cohort of postmenopausal women, adherence to a healthy lifestyle was associated with a reduced risk of postmenopausal breast cancer, regardless of inherited genetic susceptibility.