WCRF has taken a leading role internationally in advancing the state of knowledge on the biological mechanisms underlying the associations between diet, lifestyle and body size, and cancer risk and survival, including their recently developed systematic review process for reviewing the mechanistic literature. We are delighted to have the opportunity to implement this systematic review process with funding from the WCRF, towards improving understanding on mechanisms linking body fatness to cancers of the breast, endometrium, and ovary, and towards ultimately informing strategies for prevention
– Renee Fortner
Background
Overweight and obesity are associated with a higher risk of at least 12 cancers, including breast (postmenopausal), endometrial and ovarian. However, we do not yet fully understand how or why overweight and obesity increase the risk of these cancers. Advancing this understanding is a major priority, as it may help inform strategies for interventions to reduce cancer risk and ultimately prevent many cancers. Intermediate mechanistic pathways such as (i) sex steroids like oestrogens and androgens, (ii) inflammation (iii) insulin-related factors, are likely links between body fatness and cancer risk.
There is a wealth of information in the published literature on associations between overweight and obesity and these potential intermediate mechanisms. Similarly, there are many studies published on these intermediate mechanisms and risk of breast (postmenopausal), endometrial and ovarian cancer. To date, these data have not been systematically reviewed to create an integrated summary of the evidence. We propose to use this wealth of published data to better understand the association between body fatness and risk of these cancers in women.
Aims and objectives
Our overarching aim is to systematically review the published literature to summarise the state of the science on potential mechanisms linking overweight and obesity to breast (postmenopausal), endometrial and ovarian cancer. We will achieve this aim by accomplishing three objectives:
- We will systematically review the literature linking adult body fatness to the following mechanistic pathways: (i) sex steroid hormones, (ii) inflammation, (iii) insulin and insulin-like growth factors (IGFs).
- We will systematically review the literature linking (i) sex steroid hormones, (ii) inflammation (iii) insulin and IGFs to breast (postmenopausal), endometrial, and ovarian cancer. A meta-analysis to provide summary estimates of associations across studies will be conducted where feasible.
- We will integrate the evidence from objectives 1 and 2 to provide an integrated summary of the evidence linking adult body fatness to the selected mechanistic pathways, and from these pathways to the selected cancers. We will produce a final report in the style of the WCRF’s Continuous Update Project (CUP) reports. We envision that the reviews undertaken in this project will contribute to a future comprehensive report on mechanisms linking adult body fatness to cancer risk, or be integrated into individual cancer-specific CUP reports.
How it will be done
The systematic reviews will be conducted using a framework for systematic reviews of mechanistic research developed by WCRF and the University of Bristol. Our group participated in a feasibility test of the framework, and has extensive experience in the area of breast, endometrial and ovarian cancer research, and thus is well qualified to execute the review and interpret the evidence.
Potential impact
We will provide the first comprehensive, systematic review of mechanisms underlying associations between body fatness and breast (postmenopausal), endometrial and ovarian cancer. This review of the evidence on biological mechanisms linking adiposity to these cancers will provide important data on the strength of these adiposity-cancer associations, as well as inform potential targets for interventions.
