Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study

Britton Trabert, Louise A. Brinton, Garnet L. Anderson, Ruth M. Pfeiffer, Roni T. Falk, Howard Strickler, Sarunas Sliesoraitis, Lewis H. Kuller, Margery L. Gass, Barbara J. Fuhrman, Xia Xu, Nicolas Wentzensen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). Methods: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2-and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. Conclusions: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. Impact: These findings further support the heterogeneous etiology of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)648-656
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Women's Health
Ovarian Neoplasms
Observational Studies
Estrogens
Estrone
Neoplasms
Tandem Mass Spectrometry
Serum
Liquid Chromatography
Case-Control Studies
Estradiol
Logistic Models
Hormones
Confidence Intervals

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study. / Trabert, Britton; Brinton, Louise A.; Anderson, Garnet L.; Pfeiffer, Ruth M.; Falk, Roni T.; Strickler, Howard; Sliesoraitis, Sarunas; Kuller, Lewis H.; Gass, Margery L.; Fuhrman, Barbara J.; Xu, Xia; Wentzensen, Nicolas.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 4, 01.04.2016, p. 648-656.

Research output: Contribution to journalArticle

Trabert, B, Brinton, LA, Anderson, GL, Pfeiffer, RM, Falk, RT, Strickler, H, Sliesoraitis, S, Kuller, LH, Gass, ML, Fuhrman, BJ, Xu, X & Wentzensen, N 2016, 'Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study', Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 4, pp. 648-656. https://doi.org/10.1158/1055-9965.EPI-15-1272-T
Trabert, Britton ; Brinton, Louise A. ; Anderson, Garnet L. ; Pfeiffer, Ruth M. ; Falk, Roni T. ; Strickler, Howard ; Sliesoraitis, Sarunas ; Kuller, Lewis H. ; Gass, Margery L. ; Fuhrman, Barbara J. ; Xu, Xia ; Wentzensen, Nicolas. / Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study. In: Cancer Epidemiology Biomarkers and Prevention. 2016 ; Vol. 25, No. 4. pp. 648-656.
@article{669172141fbc434ba98fd117b21e52ed,
title = "Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study",
abstract = "Background: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). Methods: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95{\%} confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2-and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. Conclusions: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. Impact: These findings further support the heterogeneous etiology of ovarian cancer.",
author = "Britton Trabert and Brinton, {Louise A.} and Anderson, {Garnet L.} and Pfeiffer, {Ruth M.} and Falk, {Roni T.} and Howard Strickler and Sarunas Sliesoraitis and Kuller, {Lewis H.} and Gass, {Margery L.} and Fuhrman, {Barbara J.} and Xia Xu and Nicolas Wentzensen",
year = "2016",
month = "4",
day = "1",
doi = "10.1158/1055-9965.EPI-15-1272-T",
language = "English (US)",
volume = "25",
pages = "648--656",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Circulating estrogens and postmenopausal ovarian cancer risk in the women's health initiative observational study

AU - Trabert, Britton

AU - Brinton, Louise A.

AU - Anderson, Garnet L.

AU - Pfeiffer, Ruth M.

AU - Falk, Roni T.

AU - Strickler, Howard

AU - Sliesoraitis, Sarunas

AU - Kuller, Lewis H.

AU - Gass, Margery L.

AU - Fuhrman, Barbara J.

AU - Xu, Xia

AU - Wentzensen, Nicolas

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). Methods: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2-and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. Conclusions: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. Impact: These findings further support the heterogeneous etiology of ovarian cancer.

AB - Background: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). Methods: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2-and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. Conclusions: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. Impact: These findings further support the heterogeneous etiology of ovarian cancer.

UR - http://www.scopus.com/inward/record.url?scp=84962393953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962393953&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-15-1272-T

DO - 10.1158/1055-9965.EPI-15-1272-T

M3 - Article

C2 - 26908437

AN - SCOPUS:84962393953

VL - 25

SP - 648

EP - 656

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 4

ER -