Polymorphisms of the DNA base excision repair geneMUTYH in head and neck cancer

Sliwinski T.

Background: Head and neck squamous cell carcinomas (HNSCC) comprise about 6% of all malignant neoplasms. The major risk factors of ­HNSCC are smoking and alcohol consumption. Genetic polymorphisms of DNA repair enzymes may lead to genetic instability and carcinogenesis. MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair (BER) pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine produced by reactive oxygen species (ROS). Aim: to perform a case-control study to test the association between polymorphism in the MUTYH gene: Tyr165Cys and head and neck cancer risk progression. Methods: Genotypes were determined in DNA from peripheral blood lymphocytes of 193 patients (among them 97 subjects with precancerous hyperplastic laryngeal lesions and 96 subjects with head and neck cancer) and 140 age, sex and ethnic-matched cancer-free controls by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Results: We found an association between head and neck cancer risk and the Tyr165Tyr variant of the MUTYH gene (OR 2.18; 95% CI 1.19–3.97). For Tyr165Tyr genotype we also observed positive correlation with cancer progression assessed by tumor size (OR 4.56; 95% CI 1.60–12.95). We did not observe any correlation between Tyr165Cys polymorphism of MUTYH gene and precancerous hyperplastic laryngeal lesions risk. Conclusion: The Tyr165Tyr polymorphic variant of the MUTYH gene may be associated with head and neck cancer in Polish population.

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