Single-nucleotide polymorphisms of the <i>IL-12</i> gene lead to a higher cancer risk: a meta-analysis based on 22,670 subjects

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 theIL-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 3 markers of cancer susceptibility.

The Contribution of Interleukin-12 Genetic Variations to Taiwanese Lung Cancer

“…The inconsistent conclusions may come from different ethics and/or populations investigated, and the genetic background, life-style, environmental exposure and immunostatus were different among the investigated subjects. Regarding IL-12A rs2243115, Shi and his colleagues failed to detect any significant association between this polymorphism and cancer risk in either the overall or any subgroup analyses in a meta-analysis in 2018 (60), which is consistent with our findings (Tables II and III).…”

SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women

“…Previously, IL-12-related genetic associations studies have centered their focus specifically in the heterodimeric IL-12 molecule (encoded by the IL12A and IL12B genes). Several meta-analyses have summarized the associations of these IL-12 genes and cancer risk [23,24,38]. For the IL12A gene, the SNPs rs568048 has been one of the most published [20,38].…”

“…Meta-analyses have shown that the cancer risk contribution of IL-12 SNPs varies in the context of the populations' genetic background [23][24][25]. Research has tried to address how these differences modulate cancer risk.…”

“…Research has tried to address how these differences modulate cancer risk. Yet, the vast majority of these genetic studies have been conducted in populations of predominantly European or Asian genetic background [24]. The Puerto Rican (PUR) population is genetically admixed, with a distinctive combination of European, African and Indigenous American, ancestral contributions [26].…”

Associations between hepatocellular carcinoma risk and rs3212227 and rs568408 polymorphisms: a systematic review and meta-analysis

“… 11 IL-12 is encoded by two genes, IL12A and IL12B , and numerous studies have demonstrated that the IL12A and IL12B genes include multiple functional polymorphic sites that might affect the occurrence and progression of non-Hodgkin lymphoma, 12 tuberculosis, 13 autoimmune disease, 14 gastric carcinoma, 15 lung carcinoma, 16 and other malignancies. 17 Tan et al. showed that the IL12A rs568408 variant may be a marker single-nucleotide polymorphism (SNP) associated with an increased risk of poor HBV clearance and HBV-related HCC development.…”