Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions

Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response.

Excess body adiposity, commonly expressed as body mass index (BMI), is a risk factor for many common adult cancers. Over the past decade, epidemiological data have shown that adiposity-cancer risk associations are specific for gender, site, geographical population, histological subtype and molecular phenotype. The biological mechanisms underpinning these associations are incompletely understood but need to take account of the specificities observed in epidemiology to better inform future prevention strategies.