Abstract 3280: 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
Authors: Xia Zhiyu , Connor Avonne E. , Baumgartner Kathy B. , Baumgartner Richard N. , Boone Stephanie D. , Hines Lisa M. , John Esther M. , Wolff Roger K. , Slattery Martha L. 
Published: July 2017

ALDH1A1 is a marker of normal tissue stem cells and cancer stem cells, where it is involved in self-renewal, differentiation and self-protection. ALDH1A1 is also associated with alcohol sensitivity and dependence, and functions in the detoxification of acetaldehyde. Few epidemiological studies have examined the association between ALDH1A1 and mortality among women with breast cancer (BC). To date, none of these studies have included Hispanic women or evaluated the modifying effect of alcohol consumption.

Using data from the Breast Cancer Health Disparities Study, we evaluated the associations between nine SNPs of ALDH1A1 (rs348481, rs168351, rs1888202, rs63319, rs722921, rs348461, rs348463, rs7027604, rs1424482) and overall mortality among 1134 Hispanic and 1160 non-Hispanic white (NHW) women diagnosed with incident invasive BC. Demographic and lifestyle factors were collected via in-person interviews. Modes of inheritance were considered for each SNP accordingly using their genotypes. Multivariate Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence interval (CIs). Models were adjusted for percentage of Native American (NA) ancestry, BC summary stage, and study site. To detect effect modification, interaction terms were created between percentage of NA ancestry (low ≤0.28 versus high &gt;0.28), alcohol consumption (ever versus never) and the SNPs. The likelihood ratio test was used to evaluate whether the interaction terms were significant. The Bonferroni correction was used to adjust for multiple comparisons.

After a median follow-up time of 11 years from BC diagnosis to death, a total of 542 deaths occurred. The following four SNPs were significantly associated with overall mortality: rs1424482 (HRCC =1.33; 95% CI 1.04-1.70), rs63319 (HRAA =1.30; 95% CI 1.06-1.60), rs7027604 (HRAA =1.37; 95% CI 1.11-1.70), and rs722921 (HRTA/AA =0.78; 95% CI 0.64-0.96). However, only rs7027604 remained significant after adjustment for multiple comparisons (Padj=0.035). Among women with low NA ancestry, rs63319 significantly increased risk of mortality (HRAA= 1.55; 95% CI 1.20-1.99), while a non-significant inverse association was observed among women of high NA ancestry. Among ever drinkers, rs1888202 significantly decreased risk of mortality (HRCG/GG=0.62; 95%CI 0.45-0.85), while a non-significant inverse association was observed among non-drinkers. The adjusted P-values for these interactions were not significant.

This study provides evidence that rs7027604 is associated with worse prognosis after BC diagnosis among Hispanic and NHW women. Future BC survival studies examining the relationship between ALDH1A1 and mortality should also explore the modifying effects of alcohol consumption with rs1888202 and NA ancestry with rs63319.

Citation Format: Zhiyu Xia, Avonne E. Connor, Kathy B. Baumgartner, Richard N. Baumgartner, Stephanie D. Boone, Lisa M. Hines, Esther M. John, Roger K. Wolff, Martha L. Slattery. 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]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3280. doi:10.1158/1538-7445.AM2017-3280