Chronic nonsteroidal anti‐inflammatory drug (NSAID) use suppresses multiple CpG islands hyper methylation (CIHM) of tumor suppressor genes in the human gastric mucosa

摘要: There have been reports showing a protective role of nonsteroidal anti-inflammatory drugs (NSAIDs) against gastrointestinal cancers. CpG island hyper methylation (CIHM) tumor suppressor genes is major event in carcinogenesis. We investigated the CIHM status non-cancerous gastric mucosa chronic NSAID users and non-users assessed effect NSAIDs on CIHM. Gastric samples were obtained from 51 180 non-users. p14(ARF), p16(INK4a), death-associated protein kinase (DAP-kinase), E-cadherin (CDH1) determined by methylation-specific PCR. high was defined as two or more islands methylated. p14, p16, CDH1, lower than (p14: vs users = 32.2%vs 9.8%, P = 0.003; p16: users = 35.0%vs 15.7%, P = 0.02; CDH1: users = 36.1%vs P = 0.0009; high: users = 44.4%vs 17.6%, P = 0.0009). use also associated with decreased number anova (R = –0.32, P < 0.0001). Multivariate logistic regression analysis adjustment for sex, age, Helicobacter pylori infection, revealed that inversely correlated all four an independent factor odds ratio [OR] = 0.17, 95% confidence interval [CI] = 0.06–0.48; OR = 0.32, 95% CI = 0.14–0.75; DAP-kinase: OR = 0.45, 95% CI = 0.22–0.92; OR = 0.18, 95% CI = 0.06–0.48; OR = 0.21, 95% CI = 0.09–0.49). No association found between duration dose NSAIDs. Chronic suppresses human mucosa. may suppressive methylation-related (Cancer Sci 2009; 100: 1192–1197)