Journal article

Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: A sequential causal mediation analysis

S Ghazaleh Dashti, Vivian Viallon, Julie A Simpson, Amalia Karahalios, Margarita Moreno-Betancur, Dallas R English, Marc J Gunter, Neil Murphy

International Journal of Cancer | WILEY | Published : 2020


Mechanisms underlying adiposity-colorectal cancer (CRC) association are incompletely understood. Using UK Biobank data, we investigated the role of C-reactive protein (CRP), hemoglobin-A1c (HbA1c) and (jointly) sex hormone-binding globulin (SHBG) and testosterone, in explaining this association. Total effect of obesity versus normal-weight (based on waist circumference, body mass index, waist-hip ratio) on CRC risk was decomposed into natural direct (NDE) and indirect (NIE) effects using sequential mediation analysis. After a median follow-up of 7.1 years, 2070 incident CRC cases (men = 1,280; postmenopausal women = 790) were recorded. For men, the adjusted risk ratio (RR) for waist circumfe..

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Awarded by Australian National Health and Medical Research Council

Awarded by French National Cancer Institute (INCa)

Awarded by Australian Research Council Discovery Early Career Award - Australian Government

Funding Acknowledgements

This research was conducted using the UK Biobank Resource under application number 25897. This work was supported by Australian National Health and Medical Research Council grants (1150591 to S.G.D. and 1104975 to J.A.S.); Melbourne Research Scholarship (to S.G.D.), and the French National Cancer Institute (INCa, grant no. 2017-127 to N.M.). M.M.B. is the recipient of an Australian Research Council Discovery Early Career Award (project number DE190101326) funded by the Australian Government. The work reported in this article was undertaken by S.G.D. while hosted by the International Agency for Research on Cancer (IARC) and funded partially by a PhD Scholarship by IARC. The funders did not influence the design of the study, analysis or interpretation of the data, the writing of this report or the decision to publish.