Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk

Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54–0.82, p