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

Embargo until
Date
2017-04-21
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
Background ALDH1A1 is a marker of both normal tissue and cancer stem cells, where it is involved in self-renewal, differentiation and self-protection. Few studies have examined the association between ALDH1A1 and mortality among breast cancer (BC) patients. None of these studies have included Hispanic women or explored interactions with alcohol consumption. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) BC cases from the Breast Cancer Health Disparities Study. Methods We evaluated the associations between nine SNPs of ALDH1A1 and mortality among 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Demographic and lifestyle factors were collected via in-person interviews. Additive, recessive, and dominant models were considered for each SNP. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age at diagnosis, percentage of Native American (NA) ancestry, BC stage, and study site. Models were further stratified by percentage of NA ancestry and alcohol consumption. Adjustment for multiple comparisons was performed using the Bonferroni correction. Results After a median follow-up time of 11 years from BC diagnosis, a total of 443 deaths occurred. The following SNPs were associated with increased all-cause mortality risk: the CC genotype of rs1424482 (HRCC=1.31; 95% CI 1.03-1.68), the AA genotype of rs63319 (HRAA=1.29; 95% CI 1.05-1.59), and the AA genotype of rs7027604 (HRAA=1.40; 95% CI 1.13-1.73). rs722921 (TA/AA vs. TT) (HRTA/AA=0.78; 95% CI 0.64-0.95) decreased risk of all-cause mortality. Only rs7027604 remained significant after adjustment for multiple comparisons (Padj=0.018). Among ever drinkers, rs1888202 decreased mortality risk (HRCG/GG=0.64; 95%CI 0.46-0.87), while no association was observed among non-drinkers (Pinteraction=0.022, Padj=0.181). Among women with low NA ancestry, rs63319 increased risk of mortality (HRAA=1.53; 95%CI 1.19-1.97), while a non-significant inverse association was observed among women of high NA ancestry (Pinteraction=0.022, Padj=0.181). Results for BC-specific mortality were not statistically significant. Conclusions We provide evidence that rs7027604 is significantly associated increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should explore the modifying effects of alcohol consumption with rs1888202 and NA ancestry with rs63319.
Description
Keywords
Breast cancer, mortality, ALDH1A1, alcohol consumption, Hispanics
Citation