DNA hypermethylation at the D17S5 locus in non-small cell lung cancers: its association with smoking history.

The aim of this study was to examine the association between DNA hypermethylation and clinicopathological features of non-small cell lung cancers (NSCLCs). The DNA methylation status at the D17S5 loci, at which a candidate tumor suppressor gene, HIC-1 (hypermethylated in cancer), was identified, of 51 paired tumor and nontumorous lung tissue specimens from NSCLC patients was examined by Southern blot analysis, using a methylation-sensitive restriction enzyme. DNA hypermethylation at this locus was found in 17 (33%) tumors and 16 (31%) nontumorous lung tissues. DNA in hypermethylation at this locus occurred more frequently in poorly than in well-differentiated tumors, especially in adenocarcinomas, and correlated significantly with the differentiation grade (P = 0.01). DNA hypermethylation at the D17S5 locus correlated significantly with the loss of heterozygosity at this locus in tumors (P = 0.01). The incidence of DNA hypermethylation was significantly higher in smokers than those who had never smoked in both tumors and nontumorous lung tissues (P = 0.03 and P = 0.01, respectively). These results suggest that DNA hypermethylation at the D17S5 locus may play a role in the development of NSCLCs in cigarette smokers.