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

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.