Lack of Association between Insulin Receptor Substrate2 rs1805097 Polymorphism and the Risk of Colorectal and Breast Cancer: A Meta-Analysis

Abstract

BackgroundInsulin receptor substrate-2 (IRS-2), a signaling adaptor protein, was involved in two cancer-related pathways (the phosphatidylinositol 3′-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathways). Several studies have evaluated the association between IRS2 rs1805097 (G>A) polymorphisms and the risk of colorectal and breast cancer. However, the results were inconsistent.Methodology/Principal FindingsA meta-analysis of seven published case-control studies (4 studies with 4798 cases and 5478 controls for colorectal cancer and 3 studies with 2108 cases and 2507 controls for breast cancer) were conducted to assess the strength of association using crude odd ratios (ORs) with 95% confidence intervals (CIs). For colorectal cancer, no obvious associations were found for all genetic models (homozygote comparison OR = 0.96, 95%CI 0.85–1.08, Pheterogeneity = 0.97; heterozygote comparison: OR = 0.91, 95%CI 0.73–1.13, Pheterogeneity<0.01; dominant model: OR = 0.92, 95%CI 0.80–1.06, Pheterogeneity = 0.05; recessive model: OR = 1.02, 95%CI 0.91–1.14, Pheterogeneity = 0.60). In the subgroup analysis by ethnicity, control source and consistency of frequency with Hardy-Weinberg equilibrium (HWE), still no significant associations were observed. For breast cancer, also no obvious associations were found for all genetic models (homozygote comparison: OR = 0.95, 95%CI 0.71–1.26, Pheterogeneity = 0.10; heterozygote comparison: OR = 1.00, 95%CI 0.89–1.14, Pheterogeneity = 0.71; dominant model: OR = 0.98, 95%CI 0.87–1.10, Pheterogeneity = 0.55; recessive model: OR = 0.95, 95%CI 0.72–1.25, Pheterogeneity = 0.07). We performed subgroup analyses by sample size and did not find an association.ConclusionsThis meta-analysis indicated that IRS2 rs1805097polymorphism was not associated with colorectal and breast cancer risk.

IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer

“…We believe our meta-analysis more robust than previous meta-analysis by Hu et al [20]. First, we included 2 extra studies and the sample size of this meta-analysis was larger than previous meta-analysis.…”

“…Previous meta-analysis by Hu et al indicated that IRS-2 rs1805097 polymorphism was not associated with CRC risk [ 20 ]. They only included 4 studies.…”

“…They only included 4 studies. To date, two studies [ 9 , 11 ] have been reported in recent years since the meta-analysis [ 20 ]. In analysis of all included studies, our meta-analysis found that rs1805097 polymorphism was associated with decreased CRC risk.…”

“…According to our data, the study [ 8 ] by Slattery et al conformed to HWE. We also conducted stratification analysis of cancer type, which was not performed by Hu et al [ 20 ]. Our data suggested that rs1805097 polymorphism was associated with a decreased risk of colon cancer.…”

No Association Between IRS2 Gly1057Asp Polymorphism and Esophageal Cancer

“…Although, there are numerous studies that have shown the functional effects of IRS2 Gly1057Asp variation on metabolic diseases, its effect on cancer susceptibility is still controversial. Yin et al showed that IRS2 Gly1057Asp variation is associated with decreased risk of colorectal cancer while Hu et al did not observe significant connection between IRS2 Gly1057Asp variation and colorectal cancer development (Hu et al, 2014;Yin et al, 2017). These differences may due to the sample size and populations.…”