Association of Interleukin-18 Gene Promoter-607 C>A and-137G>C Polymorphisms with Cancer Risk: A Meta-Analysis of 26 Studies

作者：Yang, Xin; Qiu, Man-Tang; Hu, Jing-Wen; Jiang, Feng; Li, Ming; Wang, Jie; Zhang, Qin; Yin, Rong^*; Xu, Lin

来源：PLos One, 2013, 8(9): e73671.

DOI：10.1371/journal.pone.0073671

• IL-18 PROMOTER
• SERUM INTERLEUKIN-18
• A/C POLYMORPHISM
• LUNG-CANCER
• CARCINOMA
• SUSCEPTIBILITY
• CELLS
• EXPRESSION
• PATHWAY

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, P-heterogeneity = 0.033; CA/AA vs. CC: OR = 1.17, 95% CI: 1.01, 1.34, P-heterogeneity = 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, P-heterogeneity = 0.823) and -137G>C (GC/CC vs. GG: OR = 1.57, 95% CI: 1.26, 1.96, P-heterogeneity = 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; P-heterogeneity = 0.569; -607C/-137C vs. -607C/-137G: OR = 1.14, 95% CI: 1.03, 1.27; P-heterogeneity = 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, P-heterogeneity = 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, P-heterogeneity<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.

• 出版日期2013-9-16
• 单位南京医科大学; 江苏省肿瘤防治研究所