Association between insulin receptor substrate 1 Gly972Arg polymorphism and cancer risk

Epidemiological studies investigating the association between the insulin receptor substrate 1 (IRS1) gene Gly972Arg (rs1801278) polymorphism and various carcinomas risk reported conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. A comprehensive search was conducted to identify all eligible studies of IRS1 Gly972Arg polymorphism and cancer risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. A total of 16 independent studies, including 11,776 cases and 11,654 controls, were identified. When all studies were pooled, we found a significant association between IRS1 Gly972Arg polymorphism and increased cancer risk under dominant model (OR = 1.16, 95 %CI = 1.04-1.30, P = 0.007) and allelic model (OR = 1.16, 95 %CI = 1.02-1.30, P = 0.02). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian cancer (dominant: OR = 1.55, 95 %CI = 1.17-2.05, P = 0.002; allelic: OR = 1.55, 95 %CI = 1.19-2.01, P = 0.001), breast cancer (allelic: OR = 1.12, 95 %CI = 1.00-1.26, P = 0.05), and other cancers (allelic: OR = 1.31, 95 %CI = 1.00-1.71, P = 0.05). When stratified by study types, significant associations were observed in both cohort studies (dominant: OR = 1.25, 95 %CI = 1.06-1.47, P = 0.007; allelic: OR = 1.25, 95 %CI = 1.07-1.46, P = 0.005) and case-control studies (dominant: OR = 1.15, 95 %CI = 1.01-1.31, P = 0.04). In the subgroup analyses by ethnicity, significantly increased cancer risk was suggested among both Caucasians (dominant: OR = 1.13, 95 %CI = 1.02-1.26, P = 0.02; allelic: OR = 1.13, 95 %CI = 1.03-1.25, P = 0.01) and mixed population (dominant: OR = 1.22, 95 %CI = 1.01-1.46, P = 0.04). Our investigations demonstrate that IRS1 Gly972Arg polymorphism was associated with an increased risk of cancer, and additional well-designed studies are warranted to validate these findings.