Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer
Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer
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DOI：
10.1089/dna.2007.0600
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发表时间：
2007-08-01
影响因子：
3.1
通讯作者：
Pang, Guangfu
中科院分区：
文献类型：
--
作者：
Liu, Yunguang;Lin, Na;Pang, Guangfu
已知遗传因素在前列腺癌的发展中是重要的。白细胞介素-18（IL-18）是一种多功能细胞因子，可诱导干扰素-γ的分泌，在抗肿瘤免疫中起重要作用。IL-18基因启动子中DNA序列的变化可能导致IL-18产生和/或活性的改变，因此这可以调节个体对前列腺癌的易感性。为了验证这一假设，我们研究了IL-18基因启动子-137 G/C和-607 C/A多态性及其单倍型与前列腺癌风险的关系。采用序列特异性引物-聚合酶链反应技术，对265例前列腺癌患者和280例年龄、性别相匹配的对照者的IL-18基因启动子区-137 G/C和-607 C/A两个单核苷酸多态性进行了分析。IL-18基因-137 G/C多态性在病例组和对照组中的基因型和等位基因分布差异有统计学意义。与-137 GG基因型相比，-137 GC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%可信区间（CI）：1.187-2.496; p =0.004，OR =2.181; 95% CI：1.034-4.603; p =0.037，GC和CC分别为]。与基因分型分析的结果一致，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）。本研究首次发现IL-18基因启动子区-137G/C多态性与中国人群前列腺癌相关。
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 -137G/C polymorphism and prostate cancer in a Chinese population.