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, 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. CONCLUSIONS This meta-analysis indicated that IRS2 rs1805097 polymorphism was not associated with colorectal and breast cancer risk.