CUP global framework for the review of the biologic pathways linking diet, nutrition, body weight, and physical activity with cancer incidence – updated to version 3

<ns3:p>This current framework (version 3) updates the previous one published within the WCRF Gateway on Health Open Research (publication data of version 2: 23 September 2025).</ns3:p> <ns3:p/> <ns3:p> The purpose of the Framework is to provide guidance on how to: <ns3:list list-type="bullet"> <ns3:list-item> <ns3:p>identify, review, and summarise the biological mechanisms that underpin the associations between diet, nutrition, body weight, and physical activity and cancer incidence found within CUP Global</ns3:p> </ns3:list-item> <ns3:list-item> <ns3:p>assess the strength of evidence that a given biological mechanism operates between an exposure and outcome of interest</ns3:p> </ns3:list-item> </ns3:list> These biological plausibility investigations apply to 1) exposures with an established link to cancer (strong evidence in CUP/CUP Global) and for which there are strong mechanistic data, but further work is needed (for example, a poorer understanding of the evidence for certain cancer sites); 2) exposures with a strong epidemiological link to cancer (strong evidence in CUP/CUP Global) but with limited mechanistic understanding; 3) exposures with a putative epidemiological link to cancer (limited suggestive evidence in the CUP/CUP Global) for which more robust mechanistic data would strengthen conclusions. </ns3:p> <ns3:p/> <ns3:p> Note that mechanisms evaluated using this Framework are defined as <ns3:italic>biological</ns3:italic> processes linking diet, nutrition, body weight, and physical activity and cancer incidence. <ns3:bold> The focus is primarily on molecular mechanisms but may expand to physiological mechanisms depending on the research question.</ns3:bold> </ns3:p>