Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies

The receptor for advanced glycation end products (RAGE), a member of immunoglobulin superfamily, has been proved to stimulate survival, growth, and metastatic spread of cancers cells. Evidence suggested that the 82G/S, -374T/A, and -429T/C polymorphisms in RAGE promoter region might affect the risk of cancer; however, data from epidemiological studies showed conflicting results that remain to be further clarified. This meta-analysis was performed to derive a more precise estimation of 82G/S, -374T/A, and -429T/C polymorphisms and risk of cancer. A comprehensive electronic search was conducted for articles published up until December 2, 2014, in Medline (PubMed), Embase, the Cochrane Library and Google Scholar. A total of 12 case-control articles were included in this meta-analysis, providing 3,374 cases and 3,757 controls for 82G/S, 2,936 cases and 3,338 controls for -374T/A, and 2,882 cases and 3,279 controls for -429T/C specifically. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the associations with risk of cancer. Overall, we observed significantly increased risk of cancer in relation to 82G/S (A vs. G: OR 1.321, 95 % CI 1.164-1.499, P het 0.028; AA vs. GG: OR 1.823, 95 % CI 1.541-2.157, P het < 0.001; AG vs. GG: OR 1.399, 95 % CI 1.120-1.746, P het 0.002; GA+AA vs. GG: OR 1.470, 95 % CI 1.187-1.821, P het 0.002; AA vs. GG+AG: OR 1.416, 95 % CI 1.158-1.732, P het 0.107) and reduced risk of cancer in relation to -374T/A (AA vs. TT: OR 0.818, 95 % CI 0.686-0.976, P het 0.025; A vs. T: OR 0.908, 95 % CI 0.840-0.981, P het 0.014). In subgroup analysis for 82G/S, a significantly elevated cancer risk was indicated in the population of Asian and patients with lung cancer, and for -374T/A, reduced risk was indicated in population of Caucasian and patients with lung cancer and breast cancer. But no significant association was observed between -429T/C and risk of cancer. Thus, this meta-analysis revealed that 82G/S polymorphism is associated with a significantly increased risk of cancer, while -374T/A polymorphism is associated with a reduced risk of cancers.