Association between IL-17A, -17F and MIF polymorphisms predispose to CpG island hyper-methylation in gastric cancer.
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.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
T
Nakamura
Masakatsu
M
Yamashita
Hiromi
H
Yoshioka
Daisuke
D
Okubo
Masaaki
M
Yonemura
Joh
J
Maeda
Yoshiteru
Y
Maruyama
Naoko
N
Kamano
Toshiaki
T
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Nakagawa
Yoshihito
Y
Nagasaka
Mitsuo
M
Iwata
Masami
M
Hirata
Ichiro
I
Arisawa
Tomiyasu
T
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
D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human