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

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Authors: Cheng, T. D.; Darke, A. K.; Redman, M. W.; Zirpoli, G. R.; Davis, W; Payne Ondracek, R.; Bshara, W.; Omilian, A. R.; Kratzke, R.; Reid, M. E.; Molina, J. R.; Kolesar, J. M.; Chen, Y; MacRae, R. M.; Moon, J.; Mack, P.; Gandara, D. R.; Kelly, K; Santella, R. M.; Albain, K. S.; Ambrosone, C. B.
Article Title: Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)
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 lt; .001) and ER-beta (beta = 25.9, P lt; .001) but lower total PR (beta = -42.1, P lt; .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.
Journal Title: Journal of the National Cancer Institute
ISSN: 1460-2105; 0027-8874
Publisher: . Published by Oxford University Press  
Journal Place: United States
Date Published: 2018
Language: eng
DOI/URL:

10.1093/jnci/djx260
Notes: LR: 20180317; CI: (c) The Author 2017; GR: P30 CA016056/CA/NCI NIH HHS/United States; GR: K07 CA201334/CA/NCI NIH HHS/United States; GR: UG1 CA189974/CA/NCI NIH HHS/United States; GR: U10 CA180821/CA/NCI NIH HHS/United States; GR: R01 CA106815/CA/NCI NIH HHS/United States; GR: U10 CA180888/CA/NCI NIH HHS/United States; GR: U10 CA180819/CA/NCI NIH HHS/United States; GR: P30 ES009089/ES/NIEHS NIH HHS/United States; JID: 7503089; 2017/07/21 00:00 [received]; 2017/11/08 00:00 [accepted]; 2018/01/19 06:00 [entrez]; 2018/01/19 06:00 [pubmed]; 2018/01/19 06:00 [medline]; aheadofprint