Khalili-Azad T, Razmkhah M, Ghiam A F, Doroudchi M, Talei A R, Mojtahedi Z, Ghaderi A
Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
Neoplasma. 2009;56(1):22-5. doi: 10.4149/neo_2009_01_22.
Interleukin-18 [IL-18] gene promoter polymorphism is reported to be a genetic risk factor for several types of cancer. The aims of this investigation were to evaluate and compare the frequencies of IL-18 gene promoter polymorphisms at positions -137 [G/C] and -607 [C/A] in breast cancer patients and healthy controls as well as to study the contribution of these data with clinicopathological parameters at diagnosis. The studied populations comprised 250 cases with breast carcinoma and 206 healthy subjects. IL-18 gene promoter polymorphisms at positions -137 and -607 were amplified in patient and control groups using allele specific polymerase chain reaction [AS-PCR]. The frequencies of GG, GC and CC genotypes of -137 SNP were 141 [56.4%], 96 [38.4%] and 13 [5.2%] in patients vs. 110 [53.4%], 72 [34.9%] and 24 [11.7%] in controls, respectively. A significant decrease of the CC genotype was observed in patients [p = 0.04]. The frequency of the CC genotype at position -137 was also significantly higher in patients with metastasis than non-metastatic patients [21.4% vs. 4.3%] [p = 0.02]. There was no significant association between genotype frequencies at position -607 with breast cancer or its clinicopathological parameters at diagnosis. Moreover, allelic frequencies at these positions did not contribute to breast cancer incidence. The distribution of IL-18 gene haplotypes and genotype combinations were not significantly different between patients and normal control individuals. This is the first report investigating the contribution of IL-18 gene promoter polymorphisms to breast cancer. These results suggest contrast effects of IL-18 gene in cancer induction and progression. Key words: Breast cancer, IL-18, polymorphism.
据报道，白细胞介素-18（IL-18）基因启动子多态性是多种癌症的遗传风险因素。本研究的目的是评估和比较乳腺癌患者与健康对照中IL-18基因启动子-137（G/C）和-607（C/A）位点多态性的频率，并研究这些数据与诊断时临床病理参数的关系。研究人群包括250例乳腺癌患者和206名健康受试者。使用等位基因特异性聚合酶链反应（AS-PCR）在患者组和对照组中扩增-137和-607位点的IL-18基因启动子多态性。-137单核苷酸多态性（SNP）的GG、GC和CC基因型频率在患者中分别为141（56.4%）、96（38.4%）和13（5.2%），在对照组中分别为110（53.4%）、72（34.9%）和24（11.7%）。患者中CC基因型显著降低（p = 0.04）。-137位点CC基因型的频率在有转移的患者中也显著高于无转移患者（21.4%对4.3%）（p = 0.02）。-607位点的基因型频率与乳腺癌或其诊断时的临床病理参数之间无显著关联。此外，这些位点的等位基因频率对乳腺癌发病率无贡献。患者和正常对照个体之间IL-18基因单倍型和基因型组合的分布无显著差异。这是第一份研究IL-18基因启动子多态性对乳腺癌影响的报告。这些结果提示IL-18基因在癌症诱导和进展中具有相反作用。关键词：乳腺癌；IL-18；多态性
