Promoter Methylation of Retinoic Acid Receptor Beta 2 and the Development of Second Primary Lung Cancers in Non–Small-Cell Lung Cancer

Promoter Methylation of Retinoic Acid Receptor Beta 2 and the Development of Second Primary Lung Cancers in Non–Small-Cell Lung Cancer

To investigate whether the promoter hypermethylation of retinoic acid receptor beta 2 (RARbeta2) is associated with the development of second primary lung cancers (SPLCs) differentially according to smoking status in primary non-small-cell lung cancer (NSCLC). We retrospectively analyzed the relatio...

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Bibliographic Details
Published in:Journal of clinical oncology Vol. 22; no. 17; pp. 3443 - 3450
Main Authors: JIN SEUK KIM, LEE, Haengbung, KIM, Hojoong, YOUNG MOG SHIM, HAN, Joungho, PARK, Joobae, KIM, Duk-Hwan
Format: Journal Article
Language:English
Published: Baltimore, MD American Society of Clinical Oncology 01-09-2004
Lippincott Williams & Wilkins
Subjects:
Adult
Aged
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - pathology
CpG Islands
DNA Methylation
DNA, Neoplasm - metabolism
Female
Humans
Lung Neoplasms - epidemiology
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Male
Medical sciences
Middle Aged
Neoplasms, Second Primary - epidemiology
Pneumology
Promoter Regions, Genetic
Receptors, Retinoic Acid - metabolism
Retrospective Studies
Smoking
Time Factors
Tumors
Tumors of the respiratory system and mediastinum
Lung disease
Respiratory disease
Transcription promoter
Lung cancer
Retinoid
Malignant tumor
non-small cell lung carcinoma
Bronchopulmonary malignant tumor
Cancerology
Second cancer
Primary
Bronchus disease
Methylation
Retinoic acid
Tumor cell
Biological receptor
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Description
Summary:To investigate whether the promoter hypermethylation of retinoic acid receptor beta 2 (RARbeta2) is associated with the development of second primary lung cancers (SPLCs) differentially according to smoking status in primary non-small-cell lung cancer (NSCLC). We retrospectively analyzed the relationship between RARbeta2 methylation and the SPLC development in a total of 342 NSCLCs. The methylation status of RARbeta2 was determined by using methylation-specific polymerase chain reaction. The difference in the time to SPLC development was analyzed by using the log-rank test and the Cox proportional hazards model. The median follow-up was 4.1 years. SPLCs developed in 19 (5.6%) of the 342 NSCLCs, and overall incidence rate of SPLC development was 1.54 per 100 patient-years. SPLCs did not occur in 39 patients who had not smoked. After controlling for possible confounding factors, the hazard of failure for former smokers with RARbeta2 hypermethylation was about 2.87 (95% CI, 0.92 to 13.64; P =.08) times higher compared to those without RARbeta2 methylation. However, for current smokers, hypermethylation of the RARbeta2 was found to have a protective effect against the SPLC development (hazard ratio = 0.23; 95% CI, 0.11 to 0.87; P =.03). Hypermethylation of RARbeta2 promoter had a differential effect on the development of SPLCs in NSCLC, and this was dependent on smoking status. Our study suggests that a combination of retinoids and/or a demethylating agent may be effective in the prevention of SPLCs in never-smokers and former smokers with NSCLC.
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ISSN:0732-183X
1527-7755
DOI:10.1200/JCO.2004.11.135