Impact of IL-18 gene promoter polymorphisms on renal cell carcinoma occurrence and prognosis in Chinese Han population*

Abstract

Abstract Objective Genetic polymorphisms in various inflammatory cytokines have been associated with the risk and growth or invasiveness of renal cell carcinoma (RCC). However, the molecular basis of RCC pathogenesis is unclear. The aim of this study was to explore a possible association between two IL-18 gene promoter polymorphisms, -137G/C and -607C/A, and RCC occurrence and prognosis in a Chinese Han population. Methods Chinese Han patients with RCC (n = 175) and age-matched healthy controls (n = 200) were analyzed by single nucleotide polymorphism genotyping during follow-up. Results IL-18-137G allele frequency was significantly higher in patients with lymph node metastasis (Odds ratio [OR], 3.52; 95% confidence interval [CI], 0.97-16.17; P = 0.045). The IL-18-607 CC genotype was associated with distant metastasis (OR, 2.81; 95% CI, 1.35-6.24; P = 0.025). The IL-18-137 G allele was correlated with more advanced tumor stage (OR, 1.83; 95% CI, 1.05-3.72; P = 0.026) and higher tumor grade (OR, 2.23; 95% CI, 0.78-4.12; P = 0.041). The IL-18-607 CC genotype frequency was significantly higher in patients with more advanced cancer stage (OR, 2.92; 95% CI, 1.80-6.87; P = 0.001) and higher tumor grade (OR, 2.21; 95% CI, 1.25-12.25; P = 0.035). The IL-18-607 allele was associated with more advanced cancer stage (OR, 2.47; 95% CI, 1.38-3.83; P = 0.002).Carriers of the GG genotype with the -137G/ C polymorphism had a 2.165-times higher risk of RCC progression than carriers of the GC genotype (Hazard ratio = 2.15, 95% CI, 1.270-3.687). Conclusion The IL-18-137 G allele was correlated with more advanced stage, higher tumor grade, and lymph node metastasis. IL-18 gene promoter polymorphism -137G/C may thus influence the prognosis of RCC patients.