Interleukin-18 gene promoter polymorphisms and the risk of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of ESCC in a Chinese population.

Two hundred and thirty five patients with ESCC and 250 age- and sex-matched controls, using sequence specific primers-polymerase chain reaction (PCR-SSP).

Two polymorphisms, -137 G/C and -607 C/A were in strong linkage disequilibrium (LD). There were significantly differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the -137 GG genotypes (OR = 1.91, 95% CI, 1.29-2.82, p = 0.001 and OR = 2.95, 95% CI, 1.23-7.04, p = 0.012, respectively). Consistent with the results of the genotyping analyses, the -137 C/ -607 A haplotype was associated with a significantly increased risk of ESCC as compared with the -137G/-607 C haplotype (OR = 1.61; 95% CI, 1.16-2.23; p = 0.004).

This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism may contribute represent a genetic risk factor for ESCC in a Chinese population.