title: Association between IL-17A, -17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer.
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.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Maeda
authors.forename: Naoko
authors.initials: N
authors.lastname: Maruyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kamano
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masami
authors.initials: M
authors.lastname: Iwata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D000368:Aged; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human