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

• Published in: Gene Vol. 510; no. 1; pp. 71 - 77
• Main Authors: Zhou, Liping, Yao, Fan, Luan, Hong, Wang, Yinling, Dong, Xihua, Zhou, Wenwen, Wang, Qihui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2012
• Subjects: 3' Untranslated regions; 5' Untranslated Regions; Adenylate cyclase; African Continental Ancestry Group - genetics; Alleles; Asian Continental Ancestry Group - genetics; Asians; Bioindicators; biomarkers; Cancer; Carcinogenesis; Case-Control Studies; Cervix; clinical trials; Computer programs; confidence interval; European Continental Ancestry Group - genetics; Gene Frequency; Gene polymorphism; genes; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genotype; Humans; Interleukin 12; Interleukin-12 - genetics; Interleukin-12 Subunit p35 - genetics; Interleukin-12 Subunit p40 - genetics; Meta-analysis; Neoplasms; Neoplasms - ethnology; Neoplasms - genetics; Odds Ratio; Polymorphism, Single Nucleotide; Reviews; risk; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Risk Factors; Single nucleotide polymorphism; software; Statistical analysis; OR; DHPLC; CI; Interleukin-12; IVS; HuGE; PCR-RFLP; IL-12; Neoplasms; Meta-analysis; UTR; SE; SNP; HWE; Single nucleotide polymorphism; VNTR; ARMS-PCR
• DOI: 10.1016/j.gene.2012.08.019
• ISSN: 0378-1119

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. 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. 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]: 1.02-1.27; 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. 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. ► The first meta-analysis on the association of IL-12 gene with cancer risk. ► This meta-analysis has explained the role of IL-12 gene in human cancer. ► IL-12B gene polymorphisms might be potential biomarkers for cancer risk. ► Such relationship would help to design targeting anti-cancer drugs. ► This meta-analysis will be helpful in clarifying current controversies.