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The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study

  • Epidemiology
  • Published:
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Abstract

Purpose

Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women’s Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches.

Methods

To identify candidate gene–statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study.

Results

After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches.

Conclusions

We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women’s Health Initiative.

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Acknowledgements

We thank Mary Pettinger at the WHI Clinical Coordinating Center for her help with the genotype data. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The WHI program is supported by contracts from the National Heart, Lung and Blood Institute, NIH. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A listing of WHI investigators can be found at http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf.

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Authors and Affiliations

  1. Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R, Detroit, MI, 48201, USA

    Cathryn H. Bock, Gregory Dyson, Jennifer L. Beebe-Dimmer, Michele L. Cote, Kristen Purrington & Michael S. Simon

  2. St. John Health System, Van Elslander Cancer Center, 19229 Mack Ave, Grosse Pointe Woods, MI, 48236, USA

    Allison M. Jay

  3. Department of Preventive Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 675 North St. Clair, Chicago, IL, 60611, USA

    Lifang Hou

  4. Medstar Health Research Institute and Georgetown/Howard Universities Center for Clinical and Translational Science, 6525 Belcrest Road, Suite 700, Hyattsville, MD, 20782, USA

    Barbara V. Howard

  5. Division of Hematology/Oncology, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA

    Pinkal Desai

  6. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, PO Box 19024, Seattle, WA, 98109, USA

    Ross Prentice

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  1. Cathryn H. Bock
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  2. Allison M. Jay
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  3. Gregory Dyson
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  4. Jennifer L. Beebe-Dimmer
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  11. Michael S. Simon
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Correspondence to Cathryn H. Bock.

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Bock, C.H., Jay, A.M., Dyson, G. et al. The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study. Breast Cancer Res Treat 167, 741–749 (2018). https://doi.org/10.1007/s10549-017-4521-0

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