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

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.