Abstract
Insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3) play an important role in the development and progression of renal cell carcinoma (RCC). We evaluated the association of functional polymorphisms in IGF1 and IGFBP3 with susceptibility and prognosis of RCC. We genotyped nine potentially functional polymorphisms in IGF1 and IGFBP3 and assessed their association with risk of RCC in a two-stage case-control study compromising 1027 cases and 1094 controls, and with prognosis in a cohort of 311 patients. We found rs5742714 in the 3'-UTR of IGF1 was significantly associated with risk and prognosis of RCC. In the combined set, the rs5742714 GC/CC genotypes were significantly associated with decreased risk of RCC compared with the GG genotype (OR = 0.82; 95% CI = 0.68-0.98, P = 0.002). Furthermore, patients with the rs5742714 GC/CC genotypes showed improved survival than those with the GG genotype (Log-rank P = 0.025, HR = 0.36, 95% CI = 0.14-0.93). Besides, the rs5742714 GC/CC genotypes were associated with significantly decreased expression of IGF1 mRNA and lower IGF1 serum levels. Moreover, the luciferase reporter assays revealed the potential effect of rs5742714 genotype on the binding of microRNAs to IGF1. Our findings suggest that the IGF1 polymorphism rs5742714 may be a genetic predictor of susceptibility and prognosis of RCC.