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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

  • Epidemiology
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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.

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Acknowledgements

We would like to acknowledge the contributions of the following individuals to the study: Jennifer Herrick and Sandra Edwards for data harmonization oversight. Jocelyn Koo for data management for the San Francisco Bay Area Breast Cancer Study, Dr. Tim Byers and Dr. Anna R. Giuliano for their contributions to the 4-Corners Breast Cancer Study.

Funding

The work was supported by grant CA14002 from the National Cancer Institute. The San Francisco Bay Area Breast Cancer Study was supported by grants CA63446 and CA77305 from the National Cancer Institute, grant DAMD17-96-1-6071 from the U.S. Department of Defense, and grant 7 PB-0068 from the California Breast Cancer Research Program. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section. 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000036C awarded to the Cancer Prevention Institute of California; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. The 4-Corners Breast Cancer Study was funded by grants CA078682, CA078762, CA078552, and CA078802 from the National Cancer Institute. The research also was supported by the Utah Cancer Registry, which is funded by contract N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute or endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Office E-6144, Baltimore, MD, USA

    Zhiyu Xia & Avonne E. Connor

  2. Department of Epidemiology and Population Health, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Kathy B. Baumgartner, Richard N. Baumgartner & Stephanie D. Boone

  3. Department of Biology, University of Colorado, Colorado Springs, Colorado Springs, CO, USA

    Lisa M. Hines

  4. Cancer Prevention Institute of California, Fremont, CA, USA

    Esther M. John

  5. Department of Health Research and Policy (Epidemiology), and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

    Esther M. John

  6. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Roger Wolff & Martha L. Slattery

  7. Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA

    Avonne E. Connor

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  1. Zhiyu Xia
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  2. Kathy B. Baumgartner
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  3. Richard N. Baumgartner
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  4. Stephanie D. Boone
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  8. Martha L. Slattery
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  9. Avonne E. Connor
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Correspondence to Avonne E. Connor.

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Martha L. Slattery and Avonne E. Connor are senior authors.

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Xia, Z., Baumgartner, K.B., Baumgartner, R.N. et al. 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. Breast Cancer Res Treat 168, 443–455 (2018). https://doi.org/10.1007/s10549-017-4600-2

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  • DOI: https://doi.org/10.1007/s10549-017-4600-2

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