Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study.

ABSTRACT

PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption. RESULTS: A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13-1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20-2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21-2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19-1.97). CONCLUSIONS: Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.