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The interleukin-18 gene promoter -607 A/C polymorphism contributes to non-small-cell lung cancer risk in a Chinese population.

ABSTRACT: The purpose of the present study was to determine the relationship between interleukin-18 (IL-18) -607 A/C polymorphism and the risk of non-small-cell lung cancer (NSCLC) and its impact on the serum IL-18 level. The genotyping of IL-18 -607 A/C polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the AA/AC genotype distribution in NSCLC patients was significantly higher than that of healthy controls (P=0.02). However, no significant differences were found between the two subgroups when stratified by clinical characteristics. Furthermore, serum IL-18 levels were found to be significantly higher in the NSCLC patients than in the controls (P=0.01) as detected by enzyme-linked immunosorbent assay analysis. There was no correlation between serum IL-18 levels and different genotypes. In conclusion, these findings suggest that IL-18 -607 A/C polymorphism increases the risk of NSCLC in the Chinese population, and this polymorphism could not functionally affect the IL-18 levels.

SUBMITTER: Jia Y

PROVIDER: S-EPMC4807946 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Evidence suggest that IL-18 gene polymorphisms may be risk factors for several cancers. Increasing studies investigating the association between IL-18 gene promoter polymorphisms (-607 C>A and -137G>C) and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 26 studies including 4096 cases and 5222 controls. We assessed the strength of the association of IL-18 gene promoter -607 C>A and -137G>C polymorphisms with cancer risk and performed sub-group analyses by cancer types, ethnicities, source of controls and sample size. The pooled results revealed a significant increased risk of cancer susceptibility for -607 C>A (CA vs. CC: OR = 1.19, 95%CI: 1.04, 1.37, Pheterogeneity = 0.033; CA/AA vs. CC: OR = 1.17, 95% CI: 1.01, 1.34, Pheterogeneity = 0.007), but no significant association for -137 G>C was observed with overall cancer risk. Sub-group analyses revealed that an increased risk of nasopharyngeal carcinoma was both found for -607 C>A (CA/AA vs. CC: OR = 1.32, 95% CI: 1.04, 1.69, Pheterogeneity = 0.823) and -137G>C (GC/CC vs. GG: OR = 1.57, 95%CI: 1.26, 1.96, Pheterogeneity = 0.373). Consistent with the results of the genotyping analyses, the -607A/-137C and -607C/-137C haplotypes were associated with a significantly increased risk of nasopharyngeal carcinoma as compared with the -607C/-137G haplotype (-607A/-137C vs. -607C/-137G: OR = 1.26, 95%CI: 1.13, 1.40; Pheterogeneity = 0.569; -607C/-137C vs. -607C/-137G: OR = 1.14, 95%CI: 1.03, 1.27; Pheterogeneity = 0.775). As for gastrointestinal cancer, we also found that -607 C>A polymorphism was significantly associated with increased cancer risk (CA/AA vs. CC: OR = 1.25, 95% CI: 1.05, 1.50, Pheterogeneity = 0.458). Further sub-group analysis revealed that -137G>C polymorphism contributed to cancer risk in Asians but not in Caucasians (GC/CC vs. GG: OR = 1.31, 95%CI: 1.05, 1.64, Pheterogeneity<0.001). CONCLUSIONS: The meta-analysis results suggest that IL-18 gene promoter -607 C>A polymorphism is significantly associated with overall cancer risk, especially in nasopharyngeal carcinoma and gastrointestinal cancer; and the -137 G>C polymorphism is associated with increased overall cancer risk in Asian populations and also significantly increases the risk of nasopharyngeal carcinoma.

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The interleukin-18 gene promoter -607 A/C polymorphism contributes to non-small-cell lung cancer risk in a Chinese population.

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