Association between IL-17A, -17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer

Tomomitsu Tahara, Tomoyuki Shibata, Masakatsu Nakamura, Hiromi Yamashita, Daisuke Yoshioka, Masaaki Okubo, Joh Yonemura, Yoshiteru Maeda, Naoko Maruyama, Toshiaki Kamano, Yoshio Kamiya, Hiroshi Fujita, Yoshihito Nakagawa, Mitsuo Nagasaka, Masami Iwata, Ichiro Hirata, Tomiyasu Arisawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)471-477
Number of pages7
JournalInternational Journal of Molecular Medicine
Volume25
Issue number3
DOIs
Publication statusPublished - 24-02-2010

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint Dive into the research topics of 'Association between IL-17A, -17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer'. Together they form a unique fingerprint.

  • Cite this

    Tahara, T., Shibata, T., Nakamura, M., Yamashita, H., Yoshioka, D., Okubo, M., Yonemura, J., Maeda, Y., Maruyama, N., Kamano, T., Kamiya, Y., Fujita, H., Nakagawa, Y., Nagasaka, M., Iwata, M., Hirata, I., & Arisawa, T. (2010). Association between IL-17A, -17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer. International Journal of Molecular Medicine, 25(3), 471-477. https://doi.org/10.3892/ijmm_00000367