Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas

• Published in: Oral diseases 2019-01, Vol.25 (1), p.54-63
• Main Authors: Santos, Edilmar de Moura, Santos, Hellen Bandeira de Pontes, de Matos, Felipe Rodrigues, Machado, Renato Assis, Coletta, Ricardo D., Galvão, Hébel Cavalcanti, Freitas, Roseana de Almeida
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol Drinking - adverse effects; Alleles; Cancer; Carcinogens; Carcinoma - genetics; Carcinoma, Squamous Cell - genetics; Case-Control Studies; DNA repair; DNA-Binding Proteins - genetics; Environmental factors; Genetic Predisposition to Disease; Genotype; Humans; Oral cancer; Oral carcinoma; oral squamous cell carcinoma; Oropharyngeal Neoplasms - genetics; oropharyngeal squamous cell carcinoma; Oropharyngolaryngeal carcinoma; Polymorphism, Single Nucleotide; RAD51; Rad51 Recombinase - genetics; Regression analysis; Risk Factors; Single-nucleotide polymorphism; Smoking; Smoking - adverse effects; Squamous cell carcinoma; Throat cancer; Tobacco; XRCC3
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12943

Background This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. Subjects and Methods SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene–gene (GxG) interaction and gene–environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi‐square test, and univariate and multivariate methods were applied for survival analyses. Results Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. Conclusion Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.