DNA methylation of CpG sites in the promoter regions of tumour suppressor genes is a frequently acquired epigenetic event in the pathogenesis of many human cancers. The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is a tumour suppressor gene. Methylation results in inactivation of these genes.

Maruyama and colleagues looked at the relationship between the methylation status of various genes and survival in patients with NSCLC. Surgically resected specimens from 124 patients (79 men) of median (range) age 69 (25–82) years with NSCLC were studied using PCR. The majority had early stage disease (59 stage I, 24 stage II). The frequency of methylation was highest for E-cadherin (52%) followed by RAS association domain family protein (41%), FHIT and adenomatous polyposis coli (38%), retinoic acid receptor beta and H-cadherin (27%), p16^INK4A (20%), and O⁶-methylguanine-DNA-methyltransferase (0.8%). The 5 year survival rates of the patients with FHIT methylation-positive tumours was found to be significantly shorter (31.9% v 51.4%, p = 0.03), even in those patients with early stage disease (p = 0.007). However, the methylation status of other genes was not associated with any survival difference. In a multivariate analysis, FHIT methylation-positive status was found to be independently associated with poor survival (p = 0.046).

This study shows that methylation of FHIT is an independent factor associated with poor prognosis in patients with NSCLC.