Liu Yunguang, Lin Na, Huang Li, Xu Qunqing, Pang Guangfu
Department of Scientific Research, Youjiang Medical College for Nationalities, Baise, Guangxi, People's Republic of China.
DNA Cell Biol. 2007 Aug;26(8):613-8. doi: 10.1089/dna.2007.0600.
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.
已知遗传因素在前列腺癌的发生发展中起着重要作用。白细胞介素 -18(IL -18)是一种多功能细胞因子,可诱导γ-干扰素分泌,并在抗肿瘤免疫中发挥重要作用。IL -18基因启动子的DNA序列变异可能导致IL -18产生和/或活性改变,进而调节个体对前列腺癌的易感性。为验证这一假设,我们研究了IL -18基因启动子 -137G/C和 -607C/A多态性及其单倍型与前列腺癌风险的关系。我们采用序列特异性引物 - 聚合酶链反应策略,分析了265例前列腺癌患者和280例年龄及性别匹配的对照中IL -18基因启动子 -137G/C和 -607C/A的两个单核苷酸多态性。病例组和对照组中,IL -18基因 -137G/C多态性的基因型和等位基因分布存在显著差异。与 -137GG基因型相比,-137GC和CC基因型与前列腺癌风险显著增加相关[比值比(OR)= 1.721;95%置信区间(CI):1.187 - 2.496;p = 0.004,以及OR = 2.181;95% CI:1.034 - 4.603;p = 0.037,分别对应GC和CC]。与基因分型分析结果一致,与 -137G/-607C单倍型相比,-137C/-607A单倍型与前列腺癌风险显著增加相关(OR = 1.544;95% CI,1.137 - 2.096;p = 0.005)。本研究首次在中国人群中显示了IL -18基因启动子 -137G/C多态性与前列腺癌之间的关联。