High circulating insulin-like growth factor-1 reduces the risk of renal cell carcinoma: a Mendelian randomization study. (14th April 2021)

• Record Type: Journal Article
• Authors: Chen, Meng; Tsai, Chia-Wen; Chang, Wen-Shin; Xiong, Grace Y; Xu, Yifan; Bau, Da-Tian; Gu, Jian
• Is Part Of: Carcinogenesis. Volume 42:Number 6(2021)
• Page Start: 826
• Page End: 830
• Publication Date: 2021-04-14
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgab031
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: Insulin and insulin-like growth factors play important roles in carcinogenesis. Circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have been linked to cancer susceptibility. The associations of circulating IGF-1 and IGFBP-3 with the risk of renal cell carcinoma (RCC) are inconsistent. Recent large genome-wide association studies have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. In this large case–control study consisting of 2069 RCC patients and 2052 healthy controls of European ancestry, we used a two-sample Mendelian randomization (MR) approach to investigate the associations of genetically predicted circulating IGF-1 and IGFBP-3 with RCC risk. We used an individual level data-based genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses. We found that genetically predicted IGF-1 was significantly associated with RCC risk in both the GRS analysis [odds ratio (OR) = 0.43 per SD increase, 95% confidence interval (CI), 0.34–0.53] and the IVW analysis (OR = 0.46 per SD increase, 95% CI, 0.37–0.57). Dichotomized at the median GRS value of IGF-1 in controls, individuals with high GRS had a 45% reduced RCC risk (OR = 0.55, 95% CI, 0.48–0.62) compared with those with low GRS. Genetically predicted circulating IGFBP-3 was not associated with RCC risk. This is the largest RCC study of circulating IGF-1 and IGFBP-3 to date and our data suggest a strong inverse relationship between circulating IGF-1 level and RCC risk. Abstract : This is the largest case–control study to investigate the associations of circulating IGF-1 and IGFBP-3 with the risk of renal cell carcinoma. We found a strong inverse association between genetically predicted circulating IGF-1 and the risk of renal cell carcinoma.