Association of interleukin-18 gene promoter -607 C>A and -137G>C polymorphisms with cancer risk: a meta-analysis of 26 studies.
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.


RESULTS
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.
The First Clinical College of Nanjing Medical University, Nanjing, China ; Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
Xin
X
Yang
Man-Tang
MT
Qiu
Jing-Wen
JW
Hu
Feng
F
Jiang
Ming
M
Li
Jie
J
Wang
Qin
Q
Zhang
Rong
R
Yin
Lin
L
Xu
D044466:Asian People; D002277:Carcinoma; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People
D020382:Interleukin-18