Polymorphisms in insulin pathway genes and cancer risk

Fatemeh Abedi Sarvestani; Tahereh Karimi Shayan; Arash Abdolmaleki; Asadollah Asadi

doi:10.18502/bccr.v13i4.14403

Fatemeh Abedi Sarvestani Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
Tahereh Karimi Shayan Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
Arash Abdolmaleki Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran.
Asadollah Asadi Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

DOI: https://doi.org/10.18502/bccr.v13i4.14403

Keywords: Cancer, CRC, Genotype, Insulin, Variant.

Abstract

Background: Insulin is a big hormone (5808 Da) generally produced with the aid of the pancreas. Insulin receptors (IR) are found in neurons and glial cells. Insulin resistance has been related to increased plasma insulin levels, glucose intolerance, elevated insulin-like growth factor-1 (IGF-I), glucose and free fatty acids, body mass index, and an elevated risk for colorectal cancers. Proinflammatory cytokines, boom components, and hormones secreted by adipocytes play a key role in colorectal cancer etiology. Acetyl-CoA acetyltransferase (ACAT1) mediates insulin-precipitated cell proliferation and metastatic outcomes in colorectal cancer cells. Therefore, miRNAs might serve as a biological connection between metabolic changes linked to obesity and the beginning and progression of Colorectal Cancer Cancer (CRC). Furthermore, these findings shed new light on weight problems as a CRC danger component in which miRNA dysregulation may be involved. The function of IGFs in CRC is investigated by examining the association of two genetic polymorphisms in IGFBP-3 (a G → C single nucleotide polymorphism) and IGF-1 (a cytosine-adenosine dinucleotide repeat) with CRC risk in addition to the possibility of the other interventions, including physical activity, body mass index (BMI), and the use of postmenopausal hormones. These factors can exert their effects by modifying IGF-1 and the related binding proteins (IGFBP). Furthermore, the IGFBP-3 genotype can lead to a substantial effect modifier in the association between CRC and risk factors. It has been found that functional polymorphisms in the pathway of insulin genes, including IGFBPI, INSR, INS, and insulin receptor substrates 1 and 2 (IRS1 and IRS2), can be related to CRC.