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Serum estrogen and tumor-positive estrogen receptor-alpha are strong prognostic classifiers of non-small-cell lung cancer survival in both men and women.
- Source :
-
Carcinogenesis [Carcinogenesis] 2010 Oct; Vol. 31 (10), pp. 1778-86. Date of Electronic Publication: 2010 Aug 20. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung genetics
Case-Control Studies
Cohort Studies
Cytochrome P-450 CYP1A1 genetics
Estrogen Receptor alpha genetics
Female
Humans
Lung Neoplasms blood
Lung Neoplasms genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Progesterone blood
Prognosis
RNA, Messenger analysis
Carcinoma, Non-Small-Cell Lung mortality
Estrogen Receptor alpha analysis
Estrogens blood
Lung Neoplasms mortality
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 20729390
- Full Text :
- https://doi.org/10.1093/carcin/bgq156