Approved research

An investigation of anthropometry, physical inactivity, metabolic syndrome and type-2 diabetes on colorectal cancer development.

Lay summary

Obesity, physical inactivity, metabolic syndrome (metS) and type-2 diabetes (T2DM) have all been associated with higher colorectal cancer risk. However, previous studies investigating these relationships have usually been of smaller size, and many uncertainties remain, such as what are the biological pathways which link them. In phase 1 of the study, we will quantify the relationships between obesity, physical inactivity, metS and T2DM with colorectal cancer risk. In phase 2, we will use metabolic and hormonal biomarkers measured in all UK Biobank participants to investigate the possible biological pathways through which these disorders are linked. The planned analyses will aid the understanding of the obesity/inactivity/metS/T2DM and CRC relationships. The use of the metabolic and endocrinological biomarkers will highlight mechanisms through which these factors exert an effect on colorectal carcinogenesis. Presently, these molecular pathways are poorly understood with smaller previous studies yielding inconsistent results. Elucidation of these molecular pathways may aid risk prediction and identify possible therapeutic targets for CRC. In the full cohort of 500,000 men and women, information collected from participants at the onset of the study on measurements of obesity, physical activity levels, metS, and T2DM status will be used to assess the relationships between these factors and subsequent CRC risk. Additionally, the relationships between the metabolic and hormonal biomarkers and metS, T2DM, obesity and physical activity, as well as CRC, will be assessed to shed light on the possible cancer pathways which these risk factors exert an effect. The analyses of anthropometry, physical activity, metS, and T2DM and CRC risk will be undertaken on the full cohort (phase 1). Similarly, when available in 2015, the relationships between the panel of measured biomarkers and CRC will be undertaken on the full cohort (phase 2). Mediation and pathway analyses will be undertaken at this stage to elucidate the molecular pathways which link metS, T2DM, obesity, physical inactivity with CRC risk. This proposed work will build upon previous analyses undertaken by members of our research group in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Women?s Health Initiative (WHI) studies.