Free Paper Presentation : OS-63 ; Aspirin, NSAID, and Statins and Risk of Lung Cancer: A Gene by Drug Interaction Analysis = Free Paper Presentation : OS-63 ; Aspirin, NSAID, and Statins and Risk of Lung Cancer: A Gene by Drug Interaction Analysis

다국어 초록 (Multilingual Abstract)

Background: Epidemiologic studies have been shown that the use of chemopreventive drugs may decrease cancer risk. Therefore, we aimed to investigate the effects of aspirin, NSAIDs, and statins use for reduced risk of lung cancer. We further examined whether genetic polymorphisms modify these effects. Methods: The study population consisted of 1,582 lung cancer patients and 816 controls from the Massachusetts General Hospital. SNPs were assessed in genes involved in phase II metabolism (GSTs, NAT2, EPHX, and NQO1), DNA repair (ERCC1, ERCC2, and XRCC1), DNA methylation (MTHFR C677T and A1298C), and angiogenesis (VEGF +936C＞T, -460T＞C, and +405G＞C) pathways. Results: We used logistic regression to estimate the odds ratios (OR),and after adjustment for covariates, the use of statins and aspirin were significantly associated with reduced risk of lung cancer [OR 0.74, 95% confidence interval (CI) 0.56 to 0.97 for statins and OR 0.36, 95% CI 0.27 to 0.47 for aspirin, respectively], whereas an inverse association was seen with NSAIDs. Significant modifying effects were found by NAD(P)H quinine oxidoreductase (NQO1) gene polymorphisms with the use of statins (OR 0.57, 95% CI 0.40 to 0.80 for CC versus OR 1.21, 95% CI 0.74 to 1.99 for CT or TT, P = 0.03) and by glutathione S-transferases (GSTP1) with aspirin use (OR 0.23, 95% CI 0.15 to 0.35 for AA versus OR 0.46, 95% CI 0.32 to 0.67 for AG or GG, P = 0.04). Conclusions: Our results indicate that statins and aspirin use may attenuate the risk of lung cancer and genetic polymorphism may modify these associations. Key words: chemoprevention, genetic polymorphism, lung cancer, pharmacogenetics