A Novel Functional Polymorphism, 16974 A/C, in the Interleukin-12-3′ Untranslated Region Is Associated with Risk of Glioma

Abstract

Genetic factors are important in the development of glioma. Interleukin-12 (IL-12) is a multifunctional cytokine that induces Interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member, and the present studies demonstrate that IL-27 mediates a potent antitumor activity. The aim of this study was to investigate whether IL-12 and IL-27 gene polymorphisms and their serum levels are associated with glioma. We analyzed IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, and 4730 T/C polymorphisms in 210 patients with glioma and 220 matched controls, using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing methods, while serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. Serum IL-12p40 and IL-27p28 levels were decreased in patients with glioma compared with controls (p < 0.01). There were significant differences in the genotype and allele frequencies of the IL-12 gene 16974 A/C polymorphism between the group of patients with glioma and the control group (p < 0.05). Moreover, genotypes carrying the IL-12 16974 C variant allele were associated with decreased serum IL-12p40 and IL-27p28 levels compared to the homozygous wild-type genotype in patients with glioma. The IL-12 gene 16974 A/C polymorphism may regulate expression of the serum IL-12p40 and IL-27p28, and associate with increased risk of glioma. Thus, genotypes carrying the IL-12 16974 C variant allele had a decreased ability to produce IL-12 and IL-27, which may contribute to glioma susceptibility.

Association of Interleukin-12 Polymorphisms and Serum IL-12p40 Levels with Osteosarcoma Risk

“…In the present study, we found that rs3212227 AC/CC genotypes were associated with a significantly decreased risk of osteosarcoma, which were in agreement with the studies on glioma (Zhao et al, 2009) and nasopharyngeal carcinoma (Wei et al, 2009), but not the one on bladder cancer ( Jaiswal et al, 2013). The inconsistence between the present study and previous one ( Jaiswal et al, 2013) might be due to heterogeneity of cancer etiology, the profound underlying molecular mechanisms, and/or multiple environmental exposures in different ethnicities.…”

New insights into IL-12-mediated tumor suppression

“…41 In humans, polymorphisms in the 3 0 -untranslated region of IL12A lead to decreased IL-12 production, which coincides with an increased susceptibility to develop glioblastomas. 42 Despite the remarkable anticancer activity exerted by IL-12, other members of the IL-12 family play critical roles in the regulation of tumor development (see Box 1).…”

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

“…The -964A/G polymorphism (rs153109) of IL-27p28 gene promoter was first identified in a case-control study and showed a relationship with asthma susceptibility (6). After that, several case-control studies were conducted to investigate the association between IL-27p28 gene -964A/ G polymorphism and cancer risk in Chinese population (7)(8)(9)(10)(11)(12)(13)(14). However, conflicting results were observed, which might be caused by small sample size of each individual study.…”