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


METHODS
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).


CONCLUSIONS
Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.
Tahara
Tomomitsu
T
Department of Gastroenterology, School of Medicine, Toyoake, Aichi, Japan. tomomiccyu@yahoo.co.jp
Arisawa
Tomiyasu
T
Shibata
Tomoyuki
T
Hirata
Ichiro
I
Nakano
Hiroshi
H
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR; D005838:Genotype; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*