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Genome-Wide Association Study of Circulating Estradiol, Testosterone, and Sex Hormone-Binding Globulin in Postmenopausal Women

Author

Listed:
  • Jennifer Prescott
  • Deborah J Thompson
  • Peter Kraft
  • Stephen J Chanock
  • Tina Audley
  • Judith Brown
  • Jean Leyland
  • Elizabeth Folkerd
  • Deborah Doody
  • Susan E Hankinson
  • David J Hunter
  • Kevin B Jacobs
  • Mitch Dowsett
  • David G Cox
  • Douglas F Easton
  • Immaculata De Vivo

Abstract

Genome-wide association studies (GWAS) have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG) levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS) data from the Nurses’ Health Study (NHS), and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ∼1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint β = -0.126; joint P = 2.09×10–16), downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P

Suggested Citation

  • Jennifer Prescott & Deborah J Thompson & Peter Kraft & Stephen J Chanock & Tina Audley & Judith Brown & Jean Leyland & Elizabeth Folkerd & Deborah Doody & Susan E Hankinson & David J Hunter & Kevin B , 2012. "Genome-Wide Association Study of Circulating Estradiol, Testosterone, and Sex Hormone-Binding Globulin in Postmenopausal Women," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-8, June.
    • Handle: RePEc:plo:pone00:0037815
    DOI: 10.1371/journal.pone.0037815
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    1. Claes Ohlsson & Henri Wallaschofski & Kathryn L Lunetta & Lisette Stolk & John R B Perry & Annemarie Koster & Ann-Kristin Petersen & Joel Eriksson & Terho Lehtimäki & Ilpo T Huhtaniemi & Geoffrey L Ha, 2011. "Genetic Determinants of Serum Testosterone Concentrations in Men," PLOS Genetics, Public Library of Science, vol. 7(10), pages 1-11, October.
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