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=Volume 13 - 2023

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=Background: The receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF-1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer(CRC) proliferation and differentiation. IRS a major substrate for the IGF-1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence the clinical outcome of CRC patients. 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 IGF-1 pathway genes and the risk of CRC. 
Methods: We performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 24 eligible studies with IGF-1/IGF-1R polymorphisms; and eight studies of IRS-1 and IRS-2 polymorphisms met the inclusion criteria. A total of 28 case-control studies for IGF1 rs6214, IRS1 rs1801278, and IRS2 rs1805097 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.
Results: The meta-analysis of available data for rs6214, rs1801278, and rs1805097 showed a significant association between these polymorphisms and an increased CRC risk in some of the genetic models studied(rs6214, pooled OR for CC genetic model = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278, OR for GA genetic model = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097, OR for GA genetic model = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF-1, IGF-1R, IRS-1, and IRS-2 due to heterogeneity and limited sample size. 
Conclusions: This systematic review and meta-analysis suggested that IGF-1 rs6214, IRS1 rs1801278, and IRS2 rs1805097 are associated with an increased risk of CRC. In addition, the IGF-1 rs6214 polymorphism might serve as a prognostic biomarker for CRC patients.