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


RESULTS
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.
Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32 St, 60-479 Poznań, Poland. iwziol@man.poznan.pl.
Iwona
I
Ziółkowska-Suchanek
Maria
M
Mosor
Małgorzata
M
Wierzbicka
Małgorzata
M
Rydzanicz
Marta
M
Baranowska
Jerzy
J
Nowak
D017766:Acid Anhydride Hydrolases; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D000076228:MRE11 Homologue Protein; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide
D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes