Abstract
Background and Aim: Altered expression of multidrug resistance 1 (MDR1) contributes to various cancers and its disease progression. DNA methylation is reported to present in various non-cancerous tissue as age-related phenomenon, suggesting that it occurs early in the process of tumorgenesis. We investigated the effect of MDR 1 gene promoter methylation on carcinogenesis in the stomach. Methods: In study A, we estimated the methylation ratio (MR) of the MDR1 gene promoter in both antral noncancerous mucosa and cancer lesions in 83 patients with gastric cancer (GC). In study B, we also estimated the MR in noncancerous gastric mucosa in 127 patients with GC and 82 cancer free (non-GC) subjects. Degree of histological chronic gastritis was scored according to updated Sydney systems in 200 subjects. We employed methylation-specific PCR method. Results: In the study A, MR of cancer lesions (31.3±20.5) was significantly higher than that of non noncancerous mucosa (20.9±31.3, p= 0.0004). MR was especially higher in Lauren's intestinal cancer (p<0.0001). Higher MR was also observed in more advanced stage (p=0.005), and lymph vessel invasion positive cases (p=0.002). In the study B, a significant association was found between higher methylation ratio (MR) and occurrence of GC (GC vs. non GC; 21.3±24.8 vs.10.3±14.3, H. pylori infection adjusted p = 0.001). Higher MR was also associated with occurrence of GC in both H. pylori positive (p=0.006) and negative (p=0.03) subjects. Furthermore, higher MR was closely associated with H. pylori infection status (p<0.0001), and degree of intestinal metaplasia (p=0.0008) Conclusion: The promotermethylation ofMDR1 have a significant role in carcinogenesis and tumor progression in the stomach. Furthermore, promoter methylation status of MDR1 gene in non-cancerous gastric mucosa also seems to be associated with H. pylori infection, severity of intestinal metaplasia, and GC occurrence.
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