Functional polymorphisms in the interleukin-12 gene contribute to cancer risk: Evidence from a meta-analysis of 18 case-control studies

Background: Emerging evidence from preclinical and clinical studies has shown that interleukin-12 (IL-12) has some effectiveness against endogenously arising carcinogenesis. Several potentially functional polymorphisms of IL-12 gene have been implicated in cancer risk, but individually published studies showed inconclusive results. The aim of this study was to investigate the association between IL-12 polymorphisms and cancer risk. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all articles published up to June 10, 2012 that addressed IL-12 polymorphisms and cancer risk. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 softwares. Results: Eighteen studies were included with a total of 6463 cancer cases and 7412 healthy controls. We found that the 3'UTR A>C (rs3212227) polymorphism of IL-12B gene was associated with significantly increased overall risk of cancers using random effects model (C vs A: odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.02-127; AC + CC vs AA: OR=1.20, 95%CI: 1.01-1.43). However, the 3'UTR G>A (rs568408), IVS2 T>A (rs582054) and 5'UTR T>G (rs2243115) polymorphisms of IL-12A gene did not appear to have an influence on cancer susceptibility. Further subgroup analyses showed that the 3'UTR A>C (rs3212227) polymorphism was associated with increased cancer risks in the subgroups of Asians, cervical and nasopharyngeal cancers. Conclusions: Results from the current meta-analysis indicates that the 3'UTR A>C (rs3212227) polymorphism of IL-12B gene might be a potential biomarker for cancer risk among Asians, especially for cervical and nasopharyngeal cancers. (C) 2012 Elsevier B.V. All rights reserved.