Principal Investigator: Dr Neil Murphy
Department: Department of Epidemiology and Biostatistics
Institution: Imperial College LondonTags: 8111, cancer, Colorectal, diabetes, Inactivity, Metabolism, obesity
1a: 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
1b: 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.
1c: 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.
1d: 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.