Different susceptibility of increased DNMT1 expression by exposure to tobacco smoke according to histology in primary non-small cell lung cancer.

PURPOSE: DNA methyltransferase 1 (DNMT1) is known to play an important role in the development of cancers. However, the underlying mechanisms responsible for the altered expression of DNMT1 in non-small cell lung cancers (NSCLCs) remain to be elucidated. METHODS: We investigated the relationships of mRNA expression levels of DNMT1 to the altered expression of retinoblastoma (Rb) and p53 and to the clinicopathological variables in 153 NSCLCs. The expression of DNMT1 was determined by quantitative real-time PCR, and the altered expressions of p53 and Rb were assessed by immunohistochemistry. RESULTS: The increased expression of DNMT1 was found in 47 (31%) of 153 NSCLC patients examined. The prevalence of increased DNMT1 expression was significantly different between adenocarcinoma and squamous cell carcinoma (42% vs. 19%, respectively; P = 0.004). Patients who had smoked more than 65 packyears showed a 4.17 times [95% confidence interval (CI) = 1.17-69.49; P = 0.007] higher risk of increased DNMT1 expression compared to those who had smoked less than 45 packyears in adenocarcinoma. The expressions of Rb and p53 proteins were not associated with the increased expression of DNMT1 in 153 NSCLCs (P = 0.18 and 0.54, respectively). CONCLUSIONS: The present study suggests that the susceptibility of increased DNMT1 expression by exposure to tobacco smoke may be different according to histologic subtypes in NSCLC.