Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population

Tomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Ichiro Hirata, Hiroshi Nakano

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17-0.77), advanced cancer (OR = 0.31; 95% CI = 0.13-0.73), venous invasion (OR = 0.30; 95% CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13-0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.

Original languageEnglish
Pages (from-to)1678-1682
Number of pages5
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue number10
DOIs
Publication statusPublished - 01-01-2007

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Multiple Drug Resistance
Stomach Neoplasms
Population
Genotype
P-Glycoprotein
Neoplasms
Active Biological Transport
Xenobiotics
Restriction Fragment Length Polymorphisms
Genes
Gastrointestinal Tract
Exons
Stomach
Carcinogenesis
Lymph Nodes
Epithelial Cells
Neoplasm Metastasis
Gene Expression
Polymerase Chain Reaction
Control Groups

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Tahara, Tomomitsu ; Arisawa, Tomiyasu ; Shibata, Tomoyuki ; Hirata, Ichiro ; Nakano, Hiroshi. / Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population. In: Journal of Gastroenterology and Hepatology (Australia). 2007 ; Vol. 22, No. 10. pp. 1678-1682.
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abstract = "Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95{\%} CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95{\%} CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95{\%} CI = 0.17-0.77), advanced cancer (OR = 0.31; 95{\%} CI = 0.13-0.73), venous invasion (OR = 0.30; 95{\%} CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95{\%} CI = 0.13-0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.",
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Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population. / Tahara, Tomomitsu; Arisawa, Tomiyasu; Shibata, Tomoyuki; Hirata, Ichiro; Nakano, Hiroshi.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 22, No. 10, 01.01.2007, p. 1678-1682.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population

AU - Tahara, Tomomitsu

AU - Arisawa, Tomiyasu

AU - Shibata, Tomoyuki

AU - Hirata, Ichiro

AU - Nakano, Hiroshi

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N2 - Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17-0.77), advanced cancer (OR = 0.31; 95% CI = 0.13-0.73), venous invasion (OR = 0.30; 95% CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13-0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.

AB - Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17-0.77), advanced cancer (OR = 0.31; 95% CI = 0.13-0.73), venous invasion (OR = 0.30; 95% CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13-0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.

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