Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3)

L. Beckmann, A. Hüsing, V. W. Setiawan, P. Amiano, F. Clavel-Chapelon, S. J. Chanock, D. G. Cox, R. Diver, L. Dossus, H. S. Feigelson, C. Haiman, G. Hallmans, R. B. Hayes, B. E. Henderson, R. N. Hoover, D. J. Hunter, K. Khaw, L. N. Kolonel, P. Kraft, E. LundL. Le Marchand, P. H M Peeters, E. Riboli, D. Stram, G. Thomas, M. J. Thun, R. Tumino, D. Trichopoulos, U. Vogel, W. C. Willett, M. Yeager, R. Ziegler, S. E. Hankinson, R. Kaaks

Research output: Contribution to journalArticle

Abstract

Context: Sex steroids play a central role in breast cancer development. Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. Design: Dataon700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). Setting and Participants: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. Main Outcome Measures: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. Results: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. Conclusions: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Steroid hormones
Metabolism
Prostatic Neoplasms
Dehydroepiandrosterone
Genes
Steroids
Hormones
Breast Neoplasms
Aromatase
Nutrition
Serum
Nurses
Outcome Assessment (Health Care)
Health
Androstenedione
Estrone
Gonadal Steroid Hormones
Genetic Polymorphisms
Polymorphism
Testosterone

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3). / Beckmann, L.; Hüsing, A.; Setiawan, V. W.; Amiano, P.; Clavel-Chapelon, F.; Chanock, S. J.; Cox, D. G.; Diver, R.; Dossus, L.; Feigelson, H. S.; Haiman, C.; Hallmans, G.; Hayes, R. B.; Henderson, B. E.; Hoover, R. N.; Hunter, D. J.; Khaw, K.; Kolonel, L. N.; Kraft, P.; Lund, E.; Le Marchand, L.; Peeters, P. H M; Riboli, E.; Stram, D.; Thomas, G.; Thun, M. J.; Tumino, R.; Trichopoulos, D.; Vogel, U.; Willett, W. C.; Yeager, M.; Ziegler, R.; Hankinson, S. E.; Kaaks, R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 2, 02.2011.

Research output: Contribution to journalArticle

Beckmann, L, Hüsing, A, Setiawan, VW, Amiano, P, Clavel-Chapelon, F, Chanock, SJ, Cox, DG, Diver, R, Dossus, L, Feigelson, HS, Haiman, C, Hallmans, G, Hayes, RB, Henderson, BE, Hoover, RN, Hunter, DJ, Khaw, K, Kolonel, LN, Kraft, P, Lund, E, Le Marchand, L, Peeters, PHM, Riboli, E, Stram, D, Thomas, G, Thun, MJ, Tumino, R, Trichopoulos, D, Vogel, U, Willett, WC, Yeager, M, Ziegler, R, Hankinson, SE & Kaaks, R 2011, 'Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3)', Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 2. https://doi.org/10.1210/jc.2010-0912
Beckmann, L. ; Hüsing, A. ; Setiawan, V. W. ; Amiano, P. ; Clavel-Chapelon, F. ; Chanock, S. J. ; Cox, D. G. ; Diver, R. ; Dossus, L. ; Feigelson, H. S. ; Haiman, C. ; Hallmans, G. ; Hayes, R. B. ; Henderson, B. E. ; Hoover, R. N. ; Hunter, D. J. ; Khaw, K. ; Kolonel, L. N. ; Kraft, P. ; Lund, E. ; Le Marchand, L. ; Peeters, P. H M ; Riboli, E. ; Stram, D. ; Thomas, G. ; Thun, M. J. ; Tumino, R. ; Trichopoulos, D. ; Vogel, U. ; Willett, W. C. ; Yeager, M. ; Ziegler, R. ; Hankinson, S. E. ; Kaaks, R. / Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3). In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 2.
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abstract = "Context: Sex steroids play a central role in breast cancer development. Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. Design: Dataon700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). Setting and Participants: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. Main Outcome Measures: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. Results: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. Conclusions: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.",
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T1 - Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3)

AU - Beckmann, L.

AU - Hüsing, A.

AU - Setiawan, V. W.

AU - Amiano, P.

AU - Clavel-Chapelon, F.

AU - Chanock, S. J.

AU - Cox, D. G.

AU - Diver, R.

AU - Dossus, L.

AU - Feigelson, H. S.

AU - Haiman, C.

AU - Hallmans, G.

AU - Hayes, R. B.

AU - Henderson, B. E.

AU - Hoover, R. N.

AU - Hunter, D. J.

AU - Khaw, K.

AU - Kolonel, L. N.

AU - Kraft, P.

AU - Lund, E.

AU - Le Marchand, L.

AU - Peeters, P. H M

AU - Riboli, E.

AU - Stram, D.

AU - Thomas, G.

AU - Thun, M. J.

AU - Tumino, R.

AU - Trichopoulos, D.

AU - Vogel, U.

AU - Willett, W. C.

AU - Yeager, M.

AU - Ziegler, R.

AU - Hankinson, S. E.

AU - Kaaks, R.

PY - 2011/2

Y1 - 2011/2

N2 - Context: Sex steroids play a central role in breast cancer development. Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. Design: Dataon700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). Setting and Participants: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. Main Outcome Measures: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. Results: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. Conclusions: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.

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