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白细胞介素-18基因的遗传多态性与前列腺癌风险

Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer.

作者信息

Liu Yunguang, Lin Na, Huang Li, Xu Qunqing, Pang Guangfu

机构信息

Department of Scientific Research, Youjiang Medical College for Nationalities, Baise, Guangxi, People's Republic of China.

出版信息

DNA Cell Biol. 2007 Aug;26(8):613-8. doi: 10.1089/dna.2007.0600.

Abstract

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.

摘要

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。

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