Smoking, Sex, and Non Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)

Ting-Yuan David Cheng; Amy K. Darke; Mary W. Redman; Gary R. Zirpoli; Warren Davis; Rochelle Payne Ondracek; Wiam Bshara; Angela R. Omilian; Robert Kratzke; Mary E. Reid; Julian R. Molina; Jill M. Kolesar; Yuhchyau Chen; Robert M. MacRae; James Moon; Philip Mack; David R. Gandara; Karen Kelly; Regina M. Santella; Kathy S. Albain; Christine B. Ambrosone

doi:10.1093/jnci/djx260

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Smoking, Sex, and Non Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)

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Smoking, Sex, and Non Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)

Ting-Yuan David Cheng, Amy K. Darke, Mary W. Redman, Gary R. Zirpoli, Warren Davis, Rochelle Payne Ondracek, Wiam Bshara, Angela R. Omilian, Robert Kratzke, Mary E. Reid, …

JNCI : Journal of the National Cancer Institute, Vol.110(7), pp.734-742

07/01/2018

DOI: 10.1093/jnci/djx260

PMCID: PMC6037104

PMID: 29346580

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Abstract

Background: To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods: Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. Results: In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-beta (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-alpha (regression coefficient [beta], or differences in H-scores = -15.8, P = .003) and nuclear ER-beta (beta = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-alpha (beta = 45.0, P < .001) and ER-beta (beta = 25.9, P < .001) but lower total PR (beta = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-alpha and ER-beta were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI= 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions: Lower expression of nuclear ER-beta in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-alpha and ER-beta and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.

Life Sciences & Biomedicine

Oncology

Science & Technology

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Title: Subtitle: Smoking, Sex, and Non Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)
Creators: Ting-Yuan David Cheng - Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
Amy K. Darke - Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA
Mary W. Redman - Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA
Gary R. Zirpoli - Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA
Warren Davis - Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
Rochelle Payne Ondracek - Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
Wiam Bshara - Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA
Angela R. Omilian
Robert Kratzke - University of Minnesota
Mary E. Reid - Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA
Julian R. Molina - Mayo Clin, Dept Oncol, Rochester, MN USA
Jill M. Kolesar - Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA
Yuhchyau Chen - University of Rochester
Robert M. MacRae - Ottawa Hosp Canc Ctr, Ottawa, ON, Canada
James Moon - Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA
Philip Mack - University of California, Davis
David R. Gandara - University of California, Davis
Karen Kelly - University of California, Davis
Regina M. Santella - Columbia University
Kathy S. Albain - Loyola University Chicago
Christine B. Ambrosone - Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
Resource Type: Journal article
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.110(7), pp.734-742
DOI: 10.1093/jnci/djx260
PMID: 29346580
PMCID: PMC6037104
NLM abbreviation: J Natl Cancer Inst
ISSN: 0027-8874
eISSN: 1460-2105
Publisher: Oxford Univ Press
Number of pages: 9
Grant note: P30ES009089 / National Institute of Environmental Health Sciences at the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) Breast Cancer Research Foundation R01CA106815; U10CA180888; U10CA180819; UG1CA189974; U10CA180799; U10CA180820; U10CA180821; U10CA180868; P30CA016056; K07CA201334 / National Cancer Institute at the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
Language: English
Date published: 07/01/2018
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984695797902771

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