Genetic Polymorphisms of the Interleukin-18 Gene and Risk of Prostate Cancer

Genetic factors are known to be important in the development of prostate cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-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 prostate cancer. 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 prostate cancer. We analyzed two single nucleotide polymorphisms of IL-18 gene promoter −137 G/C and −607 C/A in 265 patients with prostate cancer and 280 age- and sex-matched controls, using sequence-specific primers–polymerase chain reaction strategy. There were significant 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 prostate cancer as compared with the −137 GG genotypes [odds ratio (OR) = 1.721; 95% confidence interval (CI): 1.187–2.496; p = 0.004, and OR = 2.181; 95% CI: 1.034–4.603; p = 0.037, for GC and CC, respectively]. Consistent with the results of the genotyping analyses, the −137C/−607A haplotype was associated with a significantly increased risk of prostate cancer as compared with the −137G/−607C haplotype (OR = 1.544; 95% CI, 1.137–2.096; p = 0.005). This study shows for the first time an association between IL-18 gene promoter −137 G/C polymorphism and prostate cancer in a Chinese population.