Association Of GRM4 Gene Polymorphisms With Susceptibility And Clinicopathological Characteristics Of Osteosarcoma

Objective:Osteosarcoma is the most frequent malignant primary bone tumor that arises from mesenchymal tissue. GRM4 is expressed in human osteosarcoma cells and high expression of mGluR4 in osteosarcoma tissues is related to poor prognosis. This study was investigate to GRM4 gene single nucleotide polymorphism and osteosarcoma association studies of genetic susceptibility and clinical features.Methods:The study was conducted with 63 Chinese patients with osteosarcoma and 105 Chinese subjects in a control group. For all subjects,2-ml samples of venous blood were drew. In the case-contol study, we investigated polymorphisms in the GRM4 gene (rs2229901, rs733457 and rs 1906953) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). Osteosarcoma patients were divided into serval groups according to the clinical characteristics such as age, gender, histology, tumor location, Enneking classification, tumor metastasis and therapy,and then unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. Different survival rates of different genotypic patients with osteosarcoma were analyzed through Kaplan-Meier.Results:There were statistically significant differences in the distributions of the rs 1906953 genotypes between the cases and control group (P=0.032). However, there was no remarkable difference in the three genotypes of GRM4 gene rs2229901 and rs733457 locus between the patient group and control group (P=0.547, P=0.919). Further analysis indicated the association between rs 1906953 locus and OS was independent of gender and age. Unconditional logistic regression showed the GRM4 gene rs 1906953 was not associated with histology, tumor location or therapy; however, it was associated significantly with OS metastasis and prognosis. As for rs2229901, the analysis demonstrated that there are no any obvious differences in the relations between age, gender, invasion site, tissue type, Enneking classification, tumor metastasis, therapy and rs2229901 genotype. Survival analysis for rs 1906953 showed that the median survival time of osteosarcoma patients with the CC genotype was significantly shorter compared to the CT and TT genotypes; patients carrying CC genotype have apparently got a decrease in their recurrence-free survival time in comparison with patients carrying TT genotype. As for rs2229901, there are no any differences of the survival time among the three different genotypes of patients.Conclusion:Our data suggest that the genetic polymorphism of GRM4 gene at rs 1906953 which might increase the risk of osteosarcoma may be associated with susceptibility of osteosarcoma in a Chinese population. The patients carrying the rs1906953CC genotype are closely related to metastasis of osteosarcoma with poor clinical prognosis and shorter survival time.