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. AlbainChristine B. Ambrosone

Research output: Contribution to journalArticle

3 Citations (Scopus)

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)–a, ER-b, 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-b (P ¼ .02) and total (nuclear þ cytoplasmic) PR expression (P ¼ .02), respectively. Women had lower cytoplasmic ER-a (regression coefficient [b], or differences in H-scores ¼ –15.8, P ¼ .003) and nuclear ER-b (b ¼ –12.8, P ¼ .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-a (b ¼ 45.0, P < .001) and ER-b (b ¼ 25.9, P < .001) but lower total PR (b ¼ –42.1, P < .001) than never smokers. Higher cytoplasmic ER-a and ER-b were associated with worse survival (hazard ratio ¼ 1.73, 95% confidence interval [CI] ¼ 1.15 to 2.58, and HR ¼ 1.59, 95% CI ¼ 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions: Lower expression of nuclear ER-b in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-a and ER-b and decreasing PR protein expression May be mechanisms whereby smoking disrupts hormone pathways.

Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalJournal of the National Cancer Institute
Volume110
Issue number7
DOIs
StatePublished - Jan 1 2018

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Steroid Receptors
Non-Small Cell Lung Carcinoma
Estrogen Receptors
Smoking
Hormones
Cytoplasmic and Nuclear Receptors
Neoplasms
Progesterone Receptors
Lung Neoplasms
Confidence Intervals
Postmenopause
Survival
Oral Contraceptives
Proportional Hazards Models
Canada
Linear Models
Estrogens
Immunohistochemistry
Steroids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cheng, T. Y. D., Darke, A. K., Redman, M. W., Zirpoli, G. R., Davis, W., Ondracek, R. P., ... Ambrosone, C. B. (2018). Smoking, sex, and non–Small cell lung cancer: Steroid hormone receptors in tumor tissue (S0424). Journal of the National Cancer Institute, 110(7), 734-742. https://doi.org/10.1093/jnci/djx260

Smoking, sex, and non–Small cell lung cancer : Steroid hormone receptors in tumor tissue (S0424). / Cheng, Ting Yuan David; Darke, Amy K.; Redman, Mary W.; Zirpoli, Gary R.; Davis, Warren; Ondracek, Rochelle Payne; Bshara, Wiam; Omilian, Angela R.; Kratzke, Robert; Reid, Mary E.; Molina, Julian R; Kolesar, Jill M.; Chen, Yuhchyau; MacRae, Robert M.; Moon, James; Mack, Philip; Gandara, David R.; Kelly, Karen; Santella, Regina M.; Albain, Kathy S.; Ambrosone, Christine B.

In: Journal of the National Cancer Institute, Vol. 110, No. 7, 01.01.2018, p. 734-742.

Research output: Contribution to journalArticle

Cheng, TYD, Darke, AK, Redman, MW, Zirpoli, GR, Davis, W, Ondracek, RP, Bshara, W, Omilian, AR, Kratzke, R, Reid, ME, Molina, JR, Kolesar, JM, Chen, Y, MacRae, RM, Moon, J, Mack, P, Gandara, DR, Kelly, K, Santella, RM, Albain, KS & Ambrosone, CB 2018, 'Smoking, sex, and non–Small cell lung cancer: Steroid hormone receptors in tumor tissue (S0424)', Journal of the National Cancer Institute, vol. 110, no. 7, pp. 734-742. https://doi.org/10.1093/jnci/djx260
Cheng, Ting Yuan David ; Darke, Amy K. ; Redman, Mary W. ; Zirpoli, Gary R. ; Davis, Warren ; Ondracek, Rochelle Payne ; Bshara, Wiam ; Omilian, Angela R. ; Kratzke, Robert ; Reid, Mary E. ; Molina, Julian R ; Kolesar, Jill M. ; Chen, Yuhchyau ; MacRae, Robert M. ; Moon, James ; Mack, Philip ; Gandara, David R. ; Kelly, Karen ; Santella, Regina M. ; Albain, Kathy S. ; Ambrosone, Christine B. / Smoking, sex, and non–Small cell lung cancer : Steroid hormone receptors in tumor tissue (S0424). In: Journal of the National Cancer Institute. 2018 ; Vol. 110, No. 7. pp. 734-742.
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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)–a, ER-b, 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-b (P ¼ .02) and total (nuclear {\th} cytoplasmic) PR expression (P ¼ .02), respectively. Women had lower cytoplasmic ER-a (regression coefficient [b], or differences in H-scores ¼ –15.8, P ¼ .003) and nuclear ER-b (b ¼ –12.8, P ¼ .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-a (b ¼ 45.0, P < .001) and ER-b (b ¼ 25.9, P < .001) but lower total PR (b ¼ –42.1, P < .001) than never smokers. Higher cytoplasmic ER-a and ER-b were associated with worse survival (hazard ratio ¼ 1.73, 95{\%} confidence interval [CI] ¼ 1.15 to 2.58, and HR ¼ 1.59, 95{\%} CI ¼ 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions: Lower expression of nuclear ER-b in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-a and ER-b and decreasing PR protein expression May be mechanisms whereby smoking disrupts hormone pathways.",
author = "Cheng, {Ting Yuan David} and Darke, {Amy K.} and Redman, {Mary W.} and Zirpoli, {Gary R.} and Warren Davis and Ondracek, {Rochelle Payne} and Wiam Bshara and Omilian, {Angela R.} and Robert Kratzke and Reid, {Mary E.} and Molina, {Julian R} and Kolesar, {Jill M.} and Yuhchyau Chen and MacRae, {Robert M.} and James Moon and Philip Mack and Gandara, {David R.} and Karen Kelly and Santella, {Regina M.} and Albain, {Kathy S.} and Ambrosone, {Christine B.}",
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TY - JOUR

T1 - Smoking, sex, and non–Small cell lung cancer

T2 - Steroid hormone receptors in tumor tissue (S0424)

AU - Cheng, Ting Yuan David

AU - Darke, Amy K.

AU - Redman, Mary W.

AU - Zirpoli, Gary R.

AU - Davis, Warren

AU - Ondracek, Rochelle Payne

AU - Bshara, Wiam

AU - Omilian, Angela R.

AU - Kratzke, Robert

AU - Reid, Mary E.

AU - Molina, Julian R

AU - Kolesar, Jill M.

AU - Chen, Yuhchyau

AU - MacRae, Robert M.

AU - Moon, James

AU - Mack, Philip

AU - Gandara, David R.

AU - Kelly, Karen

AU - Santella, Regina M.

AU - Albain, Kathy S.

AU - Ambrosone, Christine B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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)–a, ER-b, 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-b (P ¼ .02) and total (nuclear þ cytoplasmic) PR expression (P ¼ .02), respectively. Women had lower cytoplasmic ER-a (regression coefficient [b], or differences in H-scores ¼ –15.8, P ¼ .003) and nuclear ER-b (b ¼ –12.8, P ¼ .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-a (b ¼ 45.0, P < .001) and ER-b (b ¼ 25.9, P < .001) but lower total PR (b ¼ –42.1, P < .001) than never smokers. Higher cytoplasmic ER-a and ER-b were associated with worse survival (hazard ratio ¼ 1.73, 95% confidence interval [CI] ¼ 1.15 to 2.58, and HR ¼ 1.59, 95% CI ¼ 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions: Lower expression of nuclear ER-b in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-a and ER-b and decreasing PR protein expression May be mechanisms whereby smoking disrupts hormone pathways.

AB - 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)–a, ER-b, 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-b (P ¼ .02) and total (nuclear þ cytoplasmic) PR expression (P ¼ .02), respectively. Women had lower cytoplasmic ER-a (regression coefficient [b], or differences in H-scores ¼ –15.8, P ¼ .003) and nuclear ER-b (b ¼ –12.8, P ¼ .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-a (b ¼ 45.0, P < .001) and ER-b (b ¼ 25.9, P < .001) but lower total PR (b ¼ –42.1, P < .001) than never smokers. Higher cytoplasmic ER-a and ER-b were associated with worse survival (hazard ratio ¼ 1.73, 95% confidence interval [CI] ¼ 1.15 to 2.58, and HR ¼ 1.59, 95% CI ¼ 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions: Lower expression of nuclear ER-b in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-a and ER-b and decreasing PR protein expression May be mechanisms whereby smoking disrupts hormone pathways.

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