AUTHOR=Cheraghpour Makan , Askari Masomeh , Tierling Sascha , Shojaee Sajad , Sadeghi Amir , Ketabi Moghadam Pardis , Khazdouz Maryam , Asadzadeh Aghdaei Hamid , Piroozkhah Moein , Nazemalhosseini-Mojarad Ehsan , Fatemi Nayeralsadat 

TITLE=A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1168942

DOI=10.3389/fonc.2023.1168942

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>The receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The <italic>IGF1</italic> receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. <italic>IRS1</italic> (Insulin receptor substrate-1), a major substrate for the <italic>IGF1R</italic>, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that <italic>IGF</italic> system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four <italic>IGF1</italic> pathway genes (<italic>IGF1</italic>, <italic>IGF1R</italic>, <italic>IRS1</italic>, and <italic>IRS2</italic>) and the risk of CRC.</p></sec><sec><title>Methods</title><p>We performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with <italic>IGF1</italic>/<italic>IGF1R</italic>, <italic>IRS1</italic> and <italic>IRS2</italic> polymorphisms; met the inclusion criteria. All case-control studies for <italic>IGF1</italic> rs6214C&gt;T, <italic>IRS1</italic> rs1801278G&gt;A, and <italic>IRS2</italic> rs1805097G&gt;A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0.</p></sec><sec><title>Results</title><p>The meta-analysis of available data for rs6214C&gt;T, rs1801278G&gt;A, and rs1805097G&gt;A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C&gt;T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G&gt;A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G&gt;A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in <italic>IGF1, IGF1R, IRS1</italic>, and <italic>IRS2</italic> due to heterogeneity and limited sample size.</p></sec><sec><title>Conclusions</title><p>This systematic review and meta-analysis provide evidence that genetic variants in <italic>IGF1</italic> rs6214C&gt;T, <italic>IRS1</italic> rs1801278G&gt;A, and <italic>IRS2</italic> rs1805097G&gt;A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.</p></sec>