Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women

Louise A. Brinton, Britton Trabert, Garnet L. Anderson, Roni T. Falk, Ashley S. Felix, Barbara J. Fuhrman, Margery L. Gass, Lewis H. Kuller, Ruth M. Pfeiffer, Thomas E. Rohan, Howard Strickler, Xia Xu, Nicolas Wentzensen

Research output: Contribution to journalArticle

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Abstract

Background: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogenmetabolites. Methods: We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk. Results: Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95%CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m2, BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01). Conclusions: Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens. Impact: These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity.

Original languageEnglish (US)
Pages (from-to)1081-1089
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2016

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Endometrial Neoplasms
Estrogens
Serum
Estradiol
Obesity
Confidence Intervals
Estrone
Women's Health
Uterus
Observational Studies
Case-Control Studies
Epidemiologic Studies
Neoplasms
Carcinogenesis
Body Mass Index
High Pressure Liquid Chromatography
Hormones

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Brinton, L. A., Trabert, B., Anderson, G. L., Falk, R. T., Felix, A. S., Fuhrman, B. J., ... Wentzensen, N. (2016). Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. Cancer Epidemiology Biomarkers and Prevention, 25(7), 1081-1089. https://doi.org/10.1158/1055-9965.EPI-16-0225

Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. / Brinton, Louise A.; Trabert, Britton; Anderson, Garnet L.; Falk, Roni T.; Felix, Ashley S.; Fuhrman, Barbara J.; Gass, Margery L.; Kuller, Lewis H.; Pfeiffer, Ruth M.; Rohan, Thomas E.; Strickler, Howard; Xu, Xia; Wentzensen, Nicolas.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 7, 01.07.2016, p. 1081-1089.

Research output: Contribution to journalArticle

Brinton, LA, Trabert, B, Anderson, GL, Falk, RT, Felix, AS, Fuhrman, BJ, Gass, ML, Kuller, LH, Pfeiffer, RM, Rohan, TE, Strickler, H, Xu, X & Wentzensen, N 2016, 'Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women', Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 7, pp. 1081-1089. https://doi.org/10.1158/1055-9965.EPI-16-0225
Brinton, Louise A. ; Trabert, Britton ; Anderson, Garnet L. ; Falk, Roni T. ; Felix, Ashley S. ; Fuhrman, Barbara J. ; Gass, Margery L. ; Kuller, Lewis H. ; Pfeiffer, Ruth M. ; Rohan, Thomas E. ; Strickler, Howard ; Xu, Xia ; Wentzensen, Nicolas. / Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. In: Cancer Epidemiology Biomarkers and Prevention. 2016 ; Vol. 25, No. 7. pp. 1081-1089.
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abstract = "Background: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogenmetabolites. Methods: We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95{\%} confidence intervals (CI) for overall and subtype-specific endometrial cancer risk. Results: Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95{\%}CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m2, BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01). Conclusions: Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens. Impact: These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity.",
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AU - Fuhrman, Barbara J.

AU - Gass, Margery L.

AU - Kuller, Lewis H.

AU - Pfeiffer, Ruth M.

AU - Rohan, Thomas E.

AU - Strickler, Howard

AU - Xu, Xia

AU - Wentzensen, Nicolas

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N2 - Background: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogenmetabolites. Methods: We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk. Results: Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95%CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m2, BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01). Conclusions: Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens. Impact: These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity.

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