Journal Article

Serum estrogen and tumor-positive estrogen receptor-alpha are strong prognostic classifiers of non-small-cell lung cancer survival in both men and women

Susan E. Olivo-Marston, Leah E. Mechanic, Steen Mollerup, Elise D. Bowman, Alan T. Remaley, Michele R. Forman, Vidar Skaug, Yun-Ling Zheng, Aage Haugen and Curtis C. Harris

in Carcinogenesis

Volume 31, issue 10, pages 1778-1786
Published in print October 2010 | ISSN: 0143-3334
Published online August 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq156
Serum estrogen and tumor-positive estrogen receptor-alpha are strong prognostic classifiers of non-small-cell lung cancer survival in both men and women

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The role of tumor estrogen receptors (ERs) and serum estrogen in lung cancer is inconclusive. We investigated the hypothesis that ERs and functional single-nucleotide polymorphisms in the estrogen biosynthesis pathway are associated with poorer lung cancer survival. Lung cancer patients (n = 305) from a National Cancer Institute-Maryland (NCI-MD) case–case cohort in the Baltimore metropolitan area were used as a test cohort. To validate, 227 cases from the NCI-MD case–control cohort and 293 cases from a Norwegian lung cancer cohort were studied. Information on demographics, tobacco and reproductive histories was collected in an interviewer-administered questionnaire. Serum estrogen, progesterone, tumor messenger RNA expression of hormone receptors and germ line DNA polymorphisms were analyzed for associations with lung cancer survival. Patients in the highest tertile of serum estrogen had worse survival in all three cohorts (P combined < 0.001). Furthermore, the variant allele of estrogen receptor alpha (ER-α) polymorphism (rs2228480) was significantly associated with increased tumor ER-α levels and worse survival in all three cohorts [hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.20– 4.01; HR = 1.76, 95% CI: 1.08–2.87 and HR = 2.85, 95% CI: 1.31–4.36). Other polymorphisms associated with lower serum estrogen correlated with improved survival. Results were independent of gender and hormone replacement therapy. We report a significant association of increased serum estrogen with poorer survival among lung cancer male and female patients. Understanding the genetic control of estrogen biosynthesis and response in lung cancer could lead to improved prognosis and therapy.

Journal Article.  7216 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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