Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women

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

Research output: Contribution to journalArticle

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-5), several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ~900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P-5 was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk.

Original languageEnglish (US)
Article numbere37815
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 4 2012
Externally publishedYes

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Sex Hormone-Binding Globulin
Genome-Wide Association Study
breast neoplasms
testosterone
Testosterone
estradiol
Estradiol
Genes
Breast Neoplasms
hormones
Hormones
nurses
Genetic Predisposition to Disease
Genetic Markers
Meta-Analysis
Joints
Nurses
Genome
Health
neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Prescott, J., Thompson, D. J., Kraft, P., Chanock, S. J., Audley, T., Brown, J., ... de Vivo, I. (2012). Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. PLoS One, 7(6), [e37815]. https://doi.org/10.1371/journal.pone.0037815

Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. / Prescott, Jennifer; Thompson, Deborah J.; Kraft, Peter; Chanock, Stephen J.; Audley, Tina; Brown, Judith; Leyland, Jean; Folkerd, Elizabeth; Doody, Deborah; Hankinson, Susan E.; Hunter, David J.; Jacobs, Kevin B.; Dowsett, Mitch; Cox, David G.; Easton, Douglas F.; de Vivo, Immaculata.

In: PLoS One, Vol. 7, No. 6, e37815, 04.06.2012.

Research output: Contribution to journalArticle

Prescott, J, Thompson, DJ, Kraft, P, Chanock, SJ, Audley, T, Brown, J, Leyland, J, Folkerd, E, Doody, D, Hankinson, SE, Hunter, DJ, Jacobs, KB, Dowsett, M, Cox, DG, Easton, DF & de Vivo, I 2012, 'Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women', PLoS One, vol. 7, no. 6, e37815. https://doi.org/10.1371/journal.pone.0037815
Prescott, Jennifer ; Thompson, Deborah J. ; Kraft, Peter ; Chanock, Stephen J. ; Audley, Tina ; Brown, Judith ; Leyland, Jean ; Folkerd, Elizabeth ; Doody, Deborah ; Hankinson, Susan E. ; Hunter, David J. ; Jacobs, Kevin B. ; Dowsett, Mitch ; Cox, David G. ; Easton, Douglas F. ; de Vivo, Immaculata. / Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. In: PLoS One. 2012 ; Vol. 7, No. 6.
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