Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis.
The macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. Two functional polymorphisms have been identified in the promoter region of the MIF gene. We attempted to clarify the associations of these polymorphisms with the development of gastric cancer. The study was performed in 229 patients with gastric cancer and 428 subjects with no evidence of gastric malignancies on the upper gastro-duodenal endoscopy. The severity of histological chronic gastritis was classified according to the updated Sydney system. Overall, the 5-CATT carriers had a reduced risk of developing gastric cancer (OR, 0.67; 96% CI, 0.48-0.93; p=0.015), especially the diffuse type cancer. In subjects >60 years, the adjusted risk for gastric cancer among individuals who were -173C carriers was 1.71 (range, 1.03-2.84; p=0.038) compared to the G/G homozygous genotype. The number of 7-CATT alleles was also positively correlated with the development of intestinal type gastric cancer (adjusted OR, 1.70; 95% CI, 1.02-2.58; p=0.043). In subjects <60 years, the 7/7-CATT homozygous genotype was linked with a risk for the progression of atrophic gastritis (adjusted OR, 8.74; 95% CI, 1.31-58.6; p=0.026). In addition, the number of 7-CATT alleles was significantly correlated with the activity and inflammation scores (p=0.010 and 0.030, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene are associated with the progression of gastric mucosal inflammation and the development of mucosal atrophy at an early stage in life and these genotypes may increase the risk for the subsequent development of gastric cancer, especially the intestinal type, in older subjects.
Arisawa
Tomiyasu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
Tahara
Tomomitsu
T
Shibata
Tomoyuki
T
Nagasaka
Mitsuo
M
Nakamura
Masakatsu
M
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Yoshioka
Daisuke
D
Arima
Yuko
Y
Okubo
Masaaki
M
Hirata
Ichiro
I
Nakano
Hiroshi
H
De la Cruz
Vidal
V
D000367:Age Factors; D005260:Female; D005756:Gastritis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000453:epidemiology; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
D008263:Macrophage Migration-Inhibitory Factors