Association between Gly1619ARG polymorphism of IGF2R domain 11 (rs629849) and advanced stage of oral cancer

Abstract

Insulin-like growth factor II receptor (IGF2R) degrades mitogen and hence is associated with tumor suppressor function. The aim of this study was to assess whether genetic variation in the mitogen-binding domain of IGF2R, Gly1619Arg, disrupts normal function of IGF2R and contributes to further progression and distant metastasis of localized oral squamous cell carcinoma (OSCC). Gly1619Arg polymorphism of IGF2R domain 11 (rs629849) was assessed in blood samples of 113 individuals with histology-confirmed OSCC, and IGF2R genotypes were correlated with the stage of tumor (localized; TMN stages I-II versus advanced; TMN stages III-IV). After controlling for demographic covariates and known risk factors for oral cancer, such as tobacco, alcohol, and areca nut use, threefold increased risk of advanced stage of OSCC was noted in those subjects who had one or two copies of the IGF2R-A-allele when compared with the GG genotype. In contrast, when compared with the carriers of the A-allele, the GG genotype demonstrated to be protective against advanced disease (adjusted odds ratios of 0.32). IGF2R genetic polymorphism may be associated with decreased function of IGF2 receptor there by contributing to the advancement and distant metastasis of localized oral cancer.