> On the blog: How being more active can protect women against breast cancer
Grant title
Linking physical activity to breast cancer: a systematic review of mechanistic studies
Background
Traditional epidemiological studies cannot always tell whether risk factors, such as a lack of physical activity, actually cause diseases or whether these are simply correlated. Understanding the underlying biology of risk factors and diseases can help inform whether these associations are causal.
Epidemiological research suggests that physical activity is associated with a reduced risk of breast cancer, but the biology underlying this association is not well understood. Pathways such as those involving sex hormones, insulin resistance and chronic inflammation are likely to be involved.
However, it is very hard to summarise all of the scientific research that has been conducted on these topics. Systematic review is a scientific method commonly used to synthesise evidence from published studies that have addressed a common research question. Until recently, methods had not been developed to synthesise mechanistic evidence in a systematic way.
World Cancer Research Fund (WCRF) International and the University of Bristol have developed a framework for generating an overview of biological pathways and undertaking systematic reviews of research. The framework, which has been independently assessed, provides a protocol for collecting and combining the biological research from human, animal and cell line studies.
Aims and objectives
We will use the WCRF International/University of Bristol framework to collect and combine the main biological pathways underlying the link between physical inactivity and breast cancer risk. These pathways broadly encompass:
- sex hormones, such as oestrogens
- metabolic disturbances, such as elevated blood insulin
- blood biomarkers of inflammation
The aim of stage one is to determine how many biomarkers and processes exist within each of the key pathways, and to document how many studies there are for each of these biomarkers or processes. We will use specially designed software to prioritise the biomarkers and processes for more in-depth review. The aim of stage two is to conduct comprehensive systematic reviews of the biomarkers and processes identified in stage one, across each of the key biological pathways.
How it will be done
Stage one will use TeMMPo (Text Mining for Mechanism Prioritisation), a specially designed web-based interface that allows users to quantify and visualise the published evidence relating to the biological pathways they are studying.
TeMMPo uses results from a literature search engine (PubMed) to generate graphs that illustrate the number of publications linking physical inactivity with specific biomarkers or processes identified within each biological pathway, and the quantity of evidence linking the same biomarkers or processes with breast cancer.
Three separate Sankey plots will be created, to represent each of the biological pathways we will study – sex hormones, metabolic disturbances and chronic inflammation. Stage two comprises the systematic review of the evidence for biomarkers and processes identified and prioritised in stage one.
We will conduct comprehensive literature searches across a number of different search engines to ensure we find as many relevant scientific studies as we can. All of the evidence we collect and combine will be considered jointly, to arrive at an overall conclusion for the biomarkers and processes under review.
Potential impact
The proposed project will produce the most comprehensive summaries to date of key biological pathways linking physical activity with breast cancer risk. The overall impact of our project is to produce a clearer understanding of how physical activity prevents breast cancer. Such knowledge will give us a clearer picture of whether the epidemiological associations are causal.
This project may also help identify new drug targets, provide insights into possible gene-environment interactions, and ultimately inform public health initiatives. There are many different studies being undertaken around the world on physical activity and cancer; the findings from our proposed project will offer important insights that will help direct the research of others, and avoid research time and effort being spent examining biological processes that are unlikely to play a part in breast cancer development.
Grant publications
- Linking Physical Activity to Breast Cancer Risk via Insulin/Insulin-Like Growth Factor Signaling System, Part 1: The Effect of Physical Activity on the Insulin/Insulin-Like Growth Factor Signaling System (Cancer Epidemiol Biomarkers Prev, December 2022)
- Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk (Cancer Epidemiol Biomarkers Prev, December 2022)
