Association of selenoprotein and selenium pathway genetic variations with colorectal cancer risk and interaction with selenium status

摘要

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe and experimental and observational evidence suggests that this contributes to the development of several cancers (Stein-brenneretal., 2013; Méplan & Hesketh, 2014; Hughes et al., 2015; Combs, 2015). Selenium is incorporated in 25 selenoproteins with roles which are thought to help prevent carcinogenesis largely due to the role of several of these proteins in cell protection from oxidative stress, redox control and the inflammatory response (Fairweather-Tait et al., 2011; Labunskyy et al., 2014). We recently reported in a nested cohort study of 966 CRC cases and 966 matched controls that a higher Se status (ascertained by serum levels of Se and Selenoprotein P, SePP) was associated with a lower colorectal cancer (CRC) risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) (Hughes et al., 2015). Additionally, association studies have revealed that genetic variations in several of the selenoprotein genes may affect CRC risk (Méplan & Hesketh, 2014). We are currently examining the association of Se pathway gene variation (Méplan et al, 2012) with CRC risk, including the interaction of gene x Se status in disease risk modification.