Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study

Jessica L. Petrick; Roni T. Falk; Paula L. Hyland; Patrick Caron; Ruth M. Pfeiffer; Shannon N. Wood; Sanford M. Dawsey; Christian C. Abnet; Philip R. Taylor; Chantal Guillemette; Liam J. Murray; Lesley A. Anderson; Michael B. Cook

doi:10.1371/journal.pone.0190325

Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study

Jessica L. Petrick^*, Roni T. Falk, Paula L. Hyland, Patrick Caron, Ruth M. Pfeiffer, Shannon N. Wood, Sanford M. Dawsey, Christian C. Abnet, Philip R. Taylor, Chantal Guillemette, Liam J. Murray, Lesley A. Anderson, Michael B. Cook

^*Corresponding author for this work

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Abstract

Background Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Methods Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Results Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio OR_Q4 v._Q1 = 2.58, 95%CI = 1.23-5.43; P_trend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. Conclusions This first study of sex steroid hormones and EA provides tentative evidence that androgen: estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

Original language	English
Article number	e0190325
Number of pages	13
Journal	PloS ONE
Volume	13
Issue number	1
Early online date	12 Dec 2017
DOIs	https://doi.org/10.1371/journal.pone.0190325
Publication status	Published - Jan 2018

Bibliographical note

Funding: The study was supported by NIH Intramural Research Program, National Cancer Institute; Cancer Focus Northern Ireland (formerly the Ulster Cancer Foundation); the Northern Ireland R&D office; and the Health Research Board, Ireland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Petrick, J. L., Falk, R. T., Hyland, P. L., Caron, P., Pfeiffer, R. M., Wood, S. N., Dawsey, S. M., Abnet, C. C., Taylor, P. R., Guillemette, C., Murray, L. J., Anderson, L. A., & Cook, M. B. (2018). Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study. PloS ONE, 13(1), Article e0190325. https://doi.org/10.1371/journal.pone.0190325

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title = "Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study",

abstract = "Background Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Methods Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Results Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v.Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. Conclusions This first study of sex steroid hormones and EA provides tentative evidence that androgen: estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.",

author = "Petrick, {Jessica L.} and Falk, {Roni T.} and Hyland, {Paula L.} and Patrick Caron and Pfeiffer, {Ruth M.} and Wood, {Shannon N.} and Dawsey, {Sanford M.} and Abnet, {Christian C.} and Taylor, {Philip R.} and Chantal Guillemette and Murray, {Liam J.} and Anderson, {Lesley A.} and Cook, {Michael B.}",

note = "Funding: The study was supported by NIH Intramural Research Program, National Cancer Institute; Cancer Focus Northern Ireland (formerly the Ulster Cancer Foundation); the Northern Ireland R&D office; and the Health Research Board, Ireland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ",

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doi = "10.1371/journal.pone.0190325",

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AU - Falk, Roni T.

AU - Hyland, Paula L.

AU - Caron, Patrick

AU - Pfeiffer, Ruth M.

AU - Wood, Shannon N.

AU - Dawsey, Sanford M.

AU - Abnet, Christian C.

AU - Taylor, Philip R.

AU - Guillemette, Chantal

AU - Murray, Liam J.

AU - Anderson, Lesley A.

AU - Cook, Michael B.

N1 - Funding: The study was supported by NIH Intramural Research Program, National Cancer Institute; Cancer Focus Northern Ireland (formerly the Ulster Cancer Foundation); the Northern Ireland R&D office; and the Health Research Board, Ireland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Y1 - 2018/1

N2 - Background Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Methods Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Results Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v.Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. Conclusions This first study of sex steroid hormones and EA provides tentative evidence that androgen: estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

AB - Background Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Methods Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Results Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v.Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. Conclusions This first study of sex steroid hormones and EA provides tentative evidence that androgen: estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

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Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study

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