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Background  The members of MRE11/RAD50/NBN (MRN) protein complex participates in DNA double-strand break repair and DNA-damage checkpoint activation. We have previously shown that the p.I171V  NBN  gene mutation may contribute to the development of laryngeal cancer. This study tested the hypothesis that variants of the  MRE11  and  RAD50  genes, previously described as cancer risk factors, predispose to increased susceptibility to head and neck cancer.    Findings  In this study we analyzed the  RAD50  and  MRE11  genes in 358 patients: 175 with a single laryngeal cancer (LC), 115 with multiple primary tumors but one malignancy (primary or second) localized in the larynx (MPT-LC), 68 patients with multiple primary tumors localized in the head or neck (MPT) and 506 controls. No carriers of previously reported mutation in the  MRE11  or  RAD50  gene (particularly the pathogenic c.687delT) were detected in the present study. We identified the p.V127I variant (2/175 LC, 2/506 controls; OR=2.91; 95% CI 0.41-20.85) and p.V315L variant (2/115 MPT-LC, 1/506 controls; OR=8.96; 95% CI 0.81-99.68) of the  RAD50  gene.    Conclusions  Our data indicated that previously described common genetic variations in the  MRE11  and  RAD50  genes do not contribute to an increased risk of laryngeal cancer and second primary tumors localized in the head and neck. Prospective studies with larger groups of patients may reveal the possible impact of these genes in tumor occurrence.

The MRN protein complex genes: MRE11 and RAD50 and susceptibility to head and neck cancers