Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis

Tomiyasu Arisawa, Tomomitsu Tahara, Tomoyuki Shibata, Mitsuo Nagasaka, Masakatsu Nakamura, Yoshio Kamiya, Hiroshi Fujita, Daisuke Yoshioka, Yuko Arima, Masaaki Okubo, Ichiro Hirata, Hiroshi Nakano, Vidal De La Cruz

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalOncology Reports
Volume19
Issue number1
Publication statusPublished - 01-01-2008

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Macrophage Migration-Inhibitory Factors
Stomach Neoplasms
Stomach
Carcinogenesis
Genes
Genotype
Alleles
Inflammation
Intestinal Neoplasms
Atrophic Gastritis
Gastritis
Genetic Promoter Regions
Endoscopy
Atrophy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Arisawa, T., Tahara, T., Shibata, T., Nagasaka, M., Nakamura, M., Kamiya, Y., ... De La Cruz, V. (2008). Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis. Oncology Reports, 19(1), 223-228.
Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nagasaka, Mitsuo ; Nakamura, Masakatsu ; Kamiya, Yoshio ; Fujita, Hiroshi ; Yoshioka, Daisuke ; Arima, Yuko ; Okubo, Masaaki ; Hirata, Ichiro ; Nakano, Hiroshi ; De La Cruz, Vidal. / Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis. In: Oncology Reports. 2008 ; Vol. 19, No. 1. pp. 223-228.
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abstract = "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.",
author = "Tomiyasu Arisawa and Tomomitsu Tahara and Tomoyuki Shibata and Mitsuo Nagasaka and Masakatsu Nakamura and Yoshio Kamiya and Hiroshi Fujita and Daisuke Yoshioka and Yuko Arima and Masaaki Okubo and Ichiro Hirata and Hiroshi Nakano and {De La Cruz}, Vidal",
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Arisawa, T, Tahara, T, Shibata, T, Nagasaka, M, Nakamura, M, Kamiya, Y, Fujita, H, Yoshioka, D, Arima, Y, Okubo, M, Hirata, I, Nakano, H & De La Cruz, V 2008, 'Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis', Oncology Reports, vol. 19, no. 1, pp. 223-228.

Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Shibata, Tomoyuki; Nagasaka, Mitsuo; Nakamura, Masakatsu; Kamiya, Yoshio; Fujita, Hiroshi; Yoshioka, Daisuke; Arima, Yuko; Okubo, Masaaki; Hirata, Ichiro; Nakano, Hiroshi; De La Cruz, Vidal.

In: Oncology Reports, Vol. 19, No. 1, 01.01.2008, p. 223-228.

Research output: Contribution to journalArticle

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T1 - Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nagasaka, Mitsuo

AU - Nakamura, Masakatsu

AU - Kamiya, Yoshio

AU - Fujita, Hiroshi

AU - Yoshioka, Daisuke

AU - Arima, Yuko

AU - Okubo, Masaaki

AU - Hirata, Ichiro

AU - Nakano, Hiroshi

AU - De La Cruz, Vidal

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Y1 - 2008/1/1

N2 - 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.

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Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y et al. Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis. Oncology Reports. 2008 Jan 1;19(1):223-228.