Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
Int J Mol Med. 2010 Mar;25(3):471-7. doi: 10.3892/ijmm_00000367.
CpG island hyper-methylation (CIHM) is one of the major events in the gastric carcinogenesis. IL-17A, -17F and MIF have a crucial role in the gastric inflammation and carcinogenesis. Recently, we showed that the genetic polymorphisms of MIF-794-CATT repeat are associated with CIHM status in the non-neoplastic gastric mucosa. Consequently, the CIHM status in the gastric cancer tissue, in relation to IL-17A (-197G>A), -17F (7488T>C), and MIF (-173G>C and -794 tetranucleotide repeats) polymorphisms was investigated. Gastric cancer tissues were obtained from 102 patients. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific polymerase chain reaction (MSP). CIHM high was defined as three or all CpG islands methylated. We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method to detect the gene polymorphisms. We did not find significant association between CIHM status and IL-17F (7488T>C) and MIF (-173G>C) polymorphisms. However, concerning the IL-17A (-197G>A) polymorphism, we found that IL-17A G carrier (GG+GA) held a significantly higher risk of CIHM of p16 (OR=11.22, 95% CI=1.38-91.17, p=0.024) and CIHM high (OR=3.51, 95% CI=1.15-10.68, p=0.027). An association was also found between the 7-CATT repeat carrier (5/7 + 6/7 + 7/7) of the MIF polymorphism (-794-CATT) and reduced risk of CIHM of CDH1 (OR=0.36, 95% CI=0.14-0.92, p=0.032). No association was found between CHIM status and homozygote genotypes of each repeat (-794-CATT 5/5, 6/6, and 7/7). The present results provided evidence that the genetic polymorphisms of IL-17A, and MIF-794-CATT repeat are associated with CIHM status in the gastric cancer. Genetic polymorphisms of IL-17A, and MIF-794-CATT repeat may be involved in methylation-related carcinogenesis in the stomach.
CpG 岛高甲基化（CIHM）是胃癌发生的主要事件之一。IL-17A、-17F 和 MIF 在胃炎症和癌变中起着关键作用。最近，我们发现 MIF-794-CATT 重复的遗传多态性与非肿瘤性胃黏膜中的 CIHM 状态有关。因此，研究了胃癌组织中 IL-17A（-197G>A）、-17F（7488T>C）和 MIF（-173G>C 和-794 四核苷酸重复）多态性与 CIHM 状态的关系。从 102 例患者中获得胃癌组织。通过甲基化特异性聚合酶链反应（MSP）测定 p14、p16、DAP-激酶和 CDH1 基因的 CIHM。CIHM 高定义为三个或所有 CpG 岛甲基化。我们采用 PCR-SSCP（IL-17A 和-17F 的多重 PCR）方法检测基因多态性。我们没有发现 CIHM 状态与 IL-17F（7488T>C）和 MIF（-173G>C）多态性之间存在显著关联。然而，关于 IL-17A（-197G>A）多态性，我们发现 IL-17A G 携带者（GG+GA）患 p16 （OR=11.22，95%CI=1.38-91.17，p=0.024）和 CIHM 高（OR=3.51，95%CI=1.15-10.68，p=0.027）的 CIHM 风险显著增加。还发现 MIF 多态性（-794-CATT）的 7-CATT 重复携带者（5/7+6/7+7/7）与 CDH1 中 CIHM 降低的风险之间存在关联（OR=0.36，95%CI=0.14-0.92，p=0.032）。在每个重复（-794-CATT5/5、6/6 和 7/7）的纯合基因型与 CHIM 状态之间未发现关联。本研究结果表明，IL-17A 和 MIF-794-CATT 重复的遗传多态性与胃癌中的 CIHM 状态有关。IL-17A 和 MIF-794-CATT 重复的遗传多态性可能参与胃的甲基化相关癌变。
