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Background  Insulin 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 Findings  A 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, P heterogeneity  = 0.97; heterozygote comparison: OR = 0.91, 95%CI 0.73–1.13, P heterogeneity <0.01; dominant model: OR = 0.92, 95%CI 0.80–1.06, P heterogeneity  = 0.05; recessive model: OR = 1.02, 95%CI 0.91–1.14, P heterogeneity  = 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, P heterogeneity  = 0.10; heterozygote comparison: OR = 1.00, 95%CI 0.89–1.14, P heterogeneity  = 0.71; dominant model: OR = 0.98, 95%CI 0.87–1.10, P heterogeneity  = 0.55; recessive model: OR = 0.95, 95%CI 0.72–1.25, P heterogeneity  = 0.07). We performed subgroup analyses by sample size and did not find an association.    Conclusions  This meta-analysis indicated that  IRS2  rs1805097polymorphism was not associated with colorectal and breast cancer risk.

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