Retinoid X receptors (RXRs) are nuclear receptors for retinoids that play a critical role in the regulation of growth and differentiation in normal and tumor cells. Deregulation of RXR expression has been reported in non-small cell lung cancer (NSCLC); however, the mechanism underlying the impaired expression of RXRs in lung cancer is not known. Aberrant methylation of promoter CpG islands is known to be a major mechanism for inactivation of tumor suppressor genes. We investigated the methylation status of the RXR genes in 139 surgically-resected NSCLCs and correlated the results with the clinicopathologic characteristics of the patients. Methylation in the tumors was detected at RXRα (5.7%), RXRβ (4.3%), and RXRγ (23.7%). RT-PCR analysis showed that RXRγ methylation correlates with mRNA expression. Methylation of the RXRγ gene was not significantly associated with the prognosis of patients; however, when the patients are categorized by smoking status, the effect of RXRγ methylation on prognosis was significantly different between never- and ever-smokers (P = 0.003 [test for homogeneity]); specifically, RXRγ methylation was associated with a significantly worse survival in never-smokers, whereas it exhibited a better survival outcome in ever-smokers, although not statistically significant. This finding suggests that methylation-associated down-regulation of the RXRγ gene may play a differential role in the carcinogenesis of NSCLCs according to smoking status, but further studies are needed to confirm this.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4935.