Insulin growth-like factor-1 (IGF-1) and its main binding protein insulin growth-like factor binding protein 3 (IGFBP-3) play important roles in cancer development and progression. We hypothesize that circulating IGF-1 and IGFBP-3 may have significant prognostic values in renal cell carcinoma (RCC) patients. We used 1,010 histologically confirmed RCC patients in this case series study to test this hypothesis. We constructed a weighted genetic risk score (GRS) using a large panel of genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) to predict circulating IGF-1 and IGFBP-3 level, respectively. We analyzed the associations of the GRS with the prognosis of RCC patients using multivariate Cox proportional hazards model. We found significant associations between genetically predicted circulating IGF-1 level, but not IGFBP-3, and RCC prognosis. RCC patients with better prognosis had significantly higher baseline circulating IGF-1 level than those with worse prognosis. Dichotomized at the median value of GRS, patients with high IGF-1 exhibited significantly lower risks of recurrence (HR=0.81, 95% CI, 0.65-0.99, P=0.045) and death (HR=0.74, 95% CI, 0.60-0.91, P=0.004). If patients were dichotomized at the 75% value of GRS, those with the highest quarter of GRS had 27% lower risk of recurrence (OR=0.73, 95% CI, 0.55-0.96, P=0.025) and 34% lower risk of death (OR=0.66, 95% CI, 0.50-0.87, P=0.003) than the other three quarters of patients. High IGF-1/IGFBP-3 ratio was also associated with reduced risks of recurrence and survival. In conclusion, high circulating IGF-1 level and IGF-1/IGFBP-3 ratio at diagnosis is associated with better prognosis in RCC patients.
Keywords: IGF-1; IGFBP-3; Renal cell carcinoma; genetic risk score; recurrence; survival.
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