From mechanisms to outcomes
There are six areas where more research on diet, nutrition, physical activity and cancer is needed, as identified by the Expert Panel of World Cancer Research Fund’s Continuous Update Project (CUP). The six areas are:
- Biological mechanisms by which diet, nutrition and physical activity affect cancer processes
- The impact of diet, nutrition and physical activity throughout the life course on cancer risk
- Better characterisation of diet, nutrition, body composition and physical activity exposures
- Better characterisation of cancer-related outcomes
- Stronger evidence for the impact of diet, nutrition and physical activity on outcomes in cancer survivors
- Globally representative research on specific exposures and cancer
Though not yet completely understood, the last few years have seen a rapid development in the characterisation of the complex and interacting intracellular and intercellular processes that lead to cancer, and the generally consistent structural and behavioural characteristics of cancer cells. However, despite evidence of various types and from several sources implicating nutritional factors as key determinants of cancer patterns in populations, relatively little research has been devoted to methodically exploring the impact of nutrition on these fundamental biological processes.
All biological processes depend on a supply of energy and nutrients that are necessary for normal function, and a nutritional perspective would aim to characterise, in a methodical way, the tolerance of these processes to variations in the supply of energy or nutrients at the cell or tumour level, and the extent to which whole body exposures (diet, activity, body composition) impact on the tumour nutritional microenvironment.
Examining the impact of diet and nutrition in the epithelial tissue niches from which most common tumours arise, and in the emerging tumour microenvironment, offers opportunities to reveal the critical mechanisms by which diet and nutrition can both potentiate and prevent the development of cancer. The metabolic and phenotypic plasticity of cells, including myofibroblasts, immune cells and adipocytes, in microenvironmental niches, is integral to the fate of potentially malignant cells. The role of diet and specific nutrients in maintaining and perturbing appropriate metabolism and function in this microenvironmental context is a research priority.
Throughout the life course
The risk of several adult cancers varies with markers of aspects of growth and development in early life – including birthweight and adult attained height – as well as with body mass index (BMI) during or at the end of childhood growth.
Nutritional factors are key determinants of patterns of growth from conception onwards. Limitation of energy or nutrient supply acts as a potential constraint on growth, and if this occurs during particular periods of growth it can lead to adaptations in the fetus or child that may persist into adulthood, with consequences for the adult phenotype. Such phenotypical alterations include susceptibility to cardiometabolic disease and may also include susceptibility to cancer.
However, the precise mechanisms through which nutritional factors may influence growth and development, and their relation to later cancer risk, remain to be determined.
Better characterisation of exposures
In the CUP, the collation and interpretation of the evidence available in the published literature has highlighted inherent limitations of dietary measurements when it comes to precisely and accurately characterising dietary intake, body composition, relevant metabolic processes and other nutritional states, and physical activity.
Incorporating the following markers and measures into study designs could help to establish causal relationships between diet, nutrition, physical activity and disease, and to avoid bias and measurement error:
- better and/or new markers of dietary intake or metabolism and physical activity.
- more objective methods of measuring the effect of exposures, such as the use of Mendelian randomisation.
- better measures of body composition that take into account the importance of not only body fatness but also muscle mass.
Better characterisation of cancer-related outcomes
The diagnosis, characterisation and treatment of cancer is increasingly complex. Emerging understanding of molecular phenotypes enables definitions of cancers that go beyond simple anatomic classifications. Future study designs must accommodate and standardise the assessment of this phenotypic diversity so that disease endpoints are comparable. In addition, the current literature is not always consistent in the description and definition of cancer outcomes, including the genomic evolution of the tumour over time and with treatment.
Better characterisation of risk according to cancer subtypes, and studies that address the molecular variability of cancer as well as other outcomes, whether cancer-specific (for example, cancer incidence, progression and recurrence) or not (for example, other noncommunicable diseases and quality of life), are therefore important.
Stronger evidence on cancer survivors
There is emerging but still limited data on the effect of diet, nutrition and physical activity in cancer survivors, regarding outcomes, including prognosis and quality of life during and after treatment. In addition, the review of the evidence for breast cancer survivors has identified various research gaps in terms of the quality of the studies to address each phase of survival and across diverse cancer types and subtypes.
Diet, nutrition and physical activity, and their interplay with genetic, epigenetic and hormonal factors, may play an important role in influencing response to and side effects from treatment, quality of life during and after treatment, and risk of metastasis and recurrence, as well as overall and cancer-specific mortality. More research is critically needed in this area.
Globally representative research
“The international nature of our work is vital, because there are so many questions when it comes to diet, nutrition and physical activity and cancer, and there are no borders to research. They stem from better understanding the logical and causal links between nutrition and physical activity and cancer, and work towards understanding how we can create more effective interventions with cancer suvivors.”
– Dr Panagiota Mitrou, World Cancer Research Fund International’s Director of Research Funding and Science External Relations
The majority of epidemiological studies are conducted in high-income countries such as the UK, the US and Australia. There is limited or no data from some countries, especially low- and middle-income countries. Most of the evidence has been based on studies conducted in populations of European ancestry and some in Asian populations. However, there is a need for research comparing associations by ethnicity and by genetic ancestry.
Patterns of cancer incidence and prevalence vary considerably according to geographical region. Furthermore, some strong evidence for particular exposures and cancers is relevant only to specific geographic regions, such as the relationship between liver cancer and exposure to aflatoxins in parts of Africa and Asia. Both observations make the case for future studies to address the lack of data from low and middle-income countries.
This webpage is a summary.
For much more, download the full chapter.