Mendelian Randomization Analyses of Circulating Levels of Insulin-Like Growth Factor 1, Genetic Polymorphism, and Their Associations with Colorectal Cancer
Mendelian Randomization Analyses of Circulating Levels of Insulin-Like Growth Factor 1, Genetic Polymorphism, and Their Associations with Colorectal Cancer
Shuangmei Zhu1, Xiang Lan1, Hanying Wang1 and Jianan Hu2*
ABSTRACT
Insulin-like growth factor 1 (IGF-1) may exert a crucial role in the progression of colorectal cancer (CRC). This work aimed to investigate the Mendelian randomization (MR) relationship between circulating level (CL) of serum IGF-1, genetic polymorphism, and their associations with CRC. Two hundred eighty-three patients with CRC at our hospital who were diagnosed during January 2019 and December 2022 were collected and marked as a cancer group (CCG). On the other hand, three hundred twenty healthy patients who underwent routine physical examinations at our hospital during the same period were selected as a control group (CTG). Furthermore, genotypes of three IGF-1 genes, rs6218, rs35767, and rs574261, were analyzed using MR analysis. In addition, association between CL of serum IGF-1 and CRC was also examined. IGF-1 rs6218 (P=0.004), rs574261 (P=0.006), and rs574261 (P=0.008) showed obvious correlations with the risk of CRC. Through a MR analysis of rs6218 and rs35767, a mutation in these genes led to a respective 1.43% (P=0.039) and 1.28% (P=0.046) increase in the risk of CRC for each additional risk allele (ARA) of IGF-1. This work revealed a close relationship between elevated IGF-1 and increased risk of CRC, and mutation of genetic polymorphism in IGF-1 may serve as a predictive marker for occurrence of CRC. These findings offered an essential groundwork for screening high-risk populations and developing personalized preventive and therapeutic approaches for CRC.
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