The role of oncostatin M receptor gene polymorphisms in bladder cancer

Abstract

BackgroundOncostatin M receptor (OSMR) represents a part of the interleukin-six (IL6) cytokine group that was discovered recently to be closely associated with cell’s growth and differentiation, inflammation, and enhancement of metastatic capacity. A comprehensive study suggests a close relationship between OSMR and papillary thyroid cancer, colorectal cancer, breast cancer, and other tumors. However, the relationship between OSMR and bladder cancer has yet to be determined.MethodsThree hundred six patients (including 142 patients with muscle-invasive bladder cancer and 164 patients with non-muscle-invasive bladder cancer) as well as 459 normal controls were included in this study. Two tag SNPs of OSMR, rs2278329, and rs2292016 were genotyped by TaqMan® SNP Genotyping Assay method and then the associations with bladder cancer were analyzed, as well as risk factors and prognosis.ResultsPatients with bladder cancer and controls did not differ significantly in terms of genotype frequencies and allele frequency distribution of rs2278329 (P = 0.77, OR = 0.97) and rs2292016 (P = 0.39, OR = 1.20) respectively. For rs2278329, no differences were found in terms of risk factors in stratified analyses. However, rs2292016 was associated with recurrence and tumor grade. GT/TT was found to increase the risk of relapse compared to the patients without allele T (GG genotype) (P = 0.016, OR = 1.878, 95% CI = 1.12–3.14) with the T allele of rs2292016 being a risk factor for recurrence (P = 0.032, OR = 0.67, 95% CI = 0.47–0.97). Besides, patients with GT genotype often present with high-grade bladder cancer (P = 0.003, OR = 2.33, 95% CI = 1.32–4.17). Multiple Cox regression analysis showed that rs2278329 and rs2292016 were related to the recurrence-free survival and overall survival in non muscle invasive bladder cancer (NMIBC) patients. For rs2278329, GA genotype could affect recurrence-free survival (P = 0.01, OR = 2.16, 95% CI = 1.17–3.98). For rs2292016, TT/GT genotype had a lower risk of death compared with GG homozygote genotype, and T was a protective factor for overall survival in bladder cancer (P = 0.029, OR = 0.22, 95% CI = 0.06–0.86).ConclusionsOSMR genotype frequencies were found to be associated with higher recurrence in bladder cancer, and it may serve as a biomarker candidate gene to predict prognosis of this disease. Further validation of OSMR as biomarker is required.