Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene.

The high incidence of multiple primary tumors (MPT) is a significant problem in head and neck tumor treatment. Recent studies suggest that carriers of heterozygous mutations in the NBS1 gene have an increased risk of malignant tumor development. The aim of our research was to assess the frequency of NBS1 mutations in patients with larynx cancer only (LC) and with MPT. The MPT group consisted of patients with one cancer localized to the larynx (primary or second) and another at another site. DNA from 175 patients with LC and 93 patients with MPT was analyzed using the single-strand conformation polymorphism method and direct sequencing. We found nine carriers of the I171V mutation among these 268 cancer patients and only one carrier among 500 population controls (0.2%). Four carriers of the I171V mutation were detected among 175 LC patients (2.3%) and five among 93 patients with MPT (5.4%). The frequencies of the I171V mutation carriers in LC and MPT patients were significantly higher than in controls (odds ratio [OR] = 11.7, confidence interval [CI] 1.3-105.2, P = 0.0175 and OR = 28.35, CI 3.27-245.7, P = 0.0005, respectively). In one individual with LC, a novel molecular variant, c.1222 A > G (p.K408E), was identified. No carriers of R215W or 657del5 NBS1 mutations were found in the present study. These findings imply that heterozygous carriers of the I171V mutation are prone to the development of larynx cancer and may, in addition, display an increased risk of second tumors at other sites.