Abstract PL05-04: Tumor biomarker discovery for aspirin chemoprevention by molecular pathological epidemiology (MPE) approach Free

Regular use of aspirin reduces incidence and mortality of various cancers. Experimental and clinical studies support a carcinogenic role of PTGS2 (cyclooxygenase-2), which is a mediator of inflammation, and a target of aspirin. Recent research using “Molecular Pathological Epidemiology (MPE)” approach (Ogino et al. J Natl Cancer Inst 2010; Chia et al. Nat Rev Clin Oncol 2012; Spitz et al. Cancer Discovery 2012, etc.) has shown that aspirin use is associated with better clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation as a molecular biomarker that predicts response to aspirin (Liao et al. NEJM 2012). Furthermore, aspirin use appears to decrease risk of BRAF-wild-type colorectal cancer, but not risk of BRAF-mutated subtype (Nishihara et al. JAMA 2013), suggesting that individuals who are susceptible to BRAF-wild-type colorectal cancer may derive benefit from aspirin use. Interestingly, the findings on aspirin use and molecular markers (BRAF and PIK3CA) in relation to cancer incidence and mortality appear to be inconsistent, but this may reflect changes in the tumor microenvironment during progression of neoplasia. Although there are currently not many cohorts that can replicate these intriguing findings, it is increasingly possible to design MPE database worldwide using routine molecular testing data, as molecular pathology testing is becoming routine clinical practice. In order to test chemopreventive effects of a number of anti-inflammatory drugs and their complex interactions, it is essential to build large-scale population-based databases including medication use, lifestyle factors, tumor tissue molecular pathology, and clinical outcome. Such databases can generate novel information on potential chemopreventive benefits of drugs, which can be further tested by experimental models and clinical trials.

Citation Format: Shuji Ogino. Tumor biomarker discovery for aspirin chemoprevention by molecular pathological epidemiology (MPE) approach. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL05-04.