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Association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer.

ABSTRACT: Esophageal cancer is the fourth leading cause of cancer-associated fatalities and the fourth most commonly diagnosed cancer. In addition to environmental risk factors, genetic factors may have a significant role in esophageal cancer carcinogenesis. A hospital-based case-control study was conducted to evaluate the genetic effects of functional single-nucleotide polymorphisms in the interleukin-18 (IL-18), IL-18 receptor 1 protein (IL-18R1), IL-18 receptor accessory protein (IL-18RAP) and IL-28B on the development of esophageal cancer. In total, 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for the present study. The IL-18 rs360719 A>G, IL-18R1 rs13015714 G>T, IL-18RAP rs917997 C>T and IL-28B rs8099917 T>G genotypes were determined. No association was observed between the IL-18R1 rs13015714 G>T, IL-18RAP rs917997 C>T and IL-28B rs8099917 T>G polymorphisms and the risk of ESCC. However, in stratification analyses, a significantly decreased risk of ESCC associated with the IL-18R1 rs13015714 G>T polymorphism and a significantly increased risk of ESCC associated with the IL-18RAP rs917997 C>T polymorphism was evident among male patients and patients who smoked or consumed alcohol. These findings highlighted that functional polymorphisms IL-18R1 rs13015714 G>T and IL-18RAP rs917997 C>T may contribute to ESCC susceptibility among these subgroups. However, the present results were obtained with a limited sample size and further epidemiological studies are warranted to clarify the role of IL-18R1 and IL-18RAP variants in the development of ESCC.

SUBMITTER: Zhu J

PROVIDER: S-EPMC4734065 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer.

Zhu Jingfeng J Liu Chao C Teng Xiao X Yin Jun J Zheng Liang L Wang Liming L Tang Weifeng W Gu Haiyong H Gu Bing B Chen Liang L

Biomedical reports 20151207 2

Esophageal cancer is the fourth leading cause of cancer-associated fatalities and the fourth most commonly diagnosed cancer. In addition to environmental risk factors, genetic factors may have a significant role in esophageal cancer carcinogenesis. A hospital-based case-control study was conducted to evaluate the genetic effects of functional single-nucleotide polymorphisms in the interleukin-18 (IL-18), IL-18 receptor 1 protein (IL-18R1), IL-18 receptor accessory protein (IL-18 ...[more]

PMID: 26893844

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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.

Dataset Information

Association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer.

Publications

Association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer.

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