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Estrogen-related genes and their contribution to racial differences in breast cancer risk

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Abstract

Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case–control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP–hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP–HT interactions in women overall within CYP1B1 (rs1800440; p het = 0.003) and within CYP17A1 (rs743572; p het = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP–HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.

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Acknowledgments

The authors would like to thank the study participants for their contribution to this research. The CARE study was supported by the National Institute of Child Health and Human Development, with additional support from the National Cancer Institute, through contracts with Emory University (N01 HD 3-3168), the Fred Hutchinson Cancer Research Center (N01 HD 2-3166), Karmanos Cancer Institute at Wayne State University (N01 HD 3-3174), the University of Pennsylvania (N01 HD-3-3176), and the University of Southern California (N01 HD 3-3175) and through an intraagency agreement with the Centers for Disease Control and Prevention (Y01 HD 7022). The research generating the AIMs data was supported by the National Cancer Institute (R03 CA 123584). KWR was supported by the Cancer Epidemiology and Biostatistics Training Grant (2 T32 CA 09168) and NINR grant K99NR012232. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or the Centers for Disease Control and Prevention. This research was supported by funding from the National Institute of Child Health and Human Development with additional support from the Centers for Disease Control and Prevention and the National Cancer Institute.

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The authors have no conflicts to disclose.

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Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Mail Stop M4-B874, Seattle, WA, 98109-1024, USA

    Kerryn W. Reding, Chu Chen, David R. Doody, Christopher S. Carlson, Christina T. Chen, John Houck, Janet R. Daling & Kathleen E. Malone

  2. Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA

    Kerryn W. Reding

  3. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Chu Chen, Christopher S. Carlson & Kathleen E. Malone

  4. Exponent, Seattle, WA, USA

    Kimberly Lowe

  5. Cancer Centers Program, National Cancer Institute, Rockville, MD, USA

    Linda K. Weiss

  6. Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Polly A. Marchbanks & Jill A. McDonald

  7. Beckman Research Institute, City of Hope, Duarte, CA, USA

    Leslie Bernstein

  8. George Washington University School of Public Health and Health Services, Washington, DC, USA

    Robert Spirtas

  9. Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    Brian L. Strom

  10. Department of Obstetrics and Gynecology, Baystate Health, Springfield, MA, USA

    Ronald T. Burkman

  11. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Michael S. Simon

  12. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Jonathan M. Liff

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  1. Kerryn W. Reding
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  2. Chu Chen
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  3. Kimberly Lowe
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  18. Kathleen E. Malone
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Correspondence to Kerryn W. Reding.

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Reding, K.W., Chen, C., Lowe, K. et al. Estrogen-related genes and their contribution to racial differences in breast cancer risk. Cancer Causes Control 23, 671–681 (2012). https://doi.org/10.1007/s10552-012-9925-x

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