Abstract
The associations between interleukin-12 (IL-12) gene polymorphisms and cancer risk have been discussed extensively, with controversial results. Therefore, we conducted the present meta-analysis to better assess the potential roles of IL-12 gene variation in cancer occurrence. Eligible articles were found via PubMed, Medline, EMBASE, Google Scholar and CNKI. Odds ratios and 95% confidence intervals were used to evaluate the associations between IL-12 gene polymorphisms and cancer risk. Thirty-one studies with 10,749 cancer patients and 11,921 healthy subjects were included in the analyses. The overall results showed that cancer risk was increased by IL-12A rs568408 (GG versus GA + AA: P = 0.004; G versus A: P = 0.005) and IL-12B rs3212227 (AA versus AC + CC: P = 0.004; CC versus AA + AC: P = 0.03; A versus C: P = 0.007) polymorphisms. Further subgroup analyses for IL-12A rs568408 and IL-12B rs3212227 revealed that the positive results could be impacted by the ethnicity of the population, cancer type and/or genotyping methods. However, we failed to detect any significant associations between the IL-12A rs2243115 polymorphism and cancer risk in either the overall or the subgroup analyses. The current study suggests that certain IL-12 gene polymorphisms serve as biological markers of cancer susceptibility.
Highlights
Cancer is a major threat to public health
It should be noted that, since there is no consensus on how to handle studies with a control group that is not in HardyWeinberg equilibrium (HWE), in this meta-analysis we did not exclude studies deviating from HWE as long as they were eligible according to the inclusion criteria and were not of poor quality (Zintzaras and Lau, 2008)
Consistent with our overall results, we found a significant association between the IL-12B rs3212227 polymorphism and cancer risk in the Asian subgroup for AA versus AC + CC (P = 0.005, Odds ratios (ORs) = 0.81, 95%confidence intervals (CIs) 0.70–0.94) and A versus C (P = 0.02, OR = 0.89, 95%CI 0.80–0.98)
Summary
Cancer is a major threat to public health. According to a recent investigation, over 14.1 million new cases and 8.2 million deaths are caused annually by cancer (Siegel et al, 2016). Lower serum IL-12 levels have been observed in patients with various types of cancer (Green et al, 2012; Stanilov et al, 2012; Tao et al, 2012; Wang et al, 2013; Fang et al., 2015), suggesting that IL-12 functions as a potent tumorsuppressive factor. Active IL-12 consists of two functional subunits, p35 and p40, which are encoded by the IL-12A and IL-12B genes, respectively (Croxford et al, 2014). Since the tumor-suppressive effect of IL-12 is well documented, functional polymorphisms of the IL-12A and IL-12B genes are thought to be good genetic candidates for cancer susceptibility
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