CanRisk programme 2016-2021

Risk stratified approaches to cancer prevention are of increasing interest at all levels of clinical care. Funded by Cancer Research UK, we are exploring the use of genetic, epidemiological, lifestyle, hormonal and imaging for predicting the likelihood of a person developing cancer, and whether knowledge of their risk will affect their behaviour. The main objective of the CanRisk programme is to develop and validate quantitative tools for cancer risk-stratification and prevention that take advantage of discoveries in both cancer genomics and epidemiology.

CanRisk aims to address the following specific research questions:

1. What improvement can be achieved in individualised risk prediction for breast, ovarian and prostate cancer, by combining data on all genetic, lifestyle/hormonal, clinical and imaging risk factors?
2. What is the accuracy of individualised breast and ovarian cancer risks for women with high risk mutations in the BRCA1 and BRCA2 genes on the basis of genetic and other risk modifying factors?
3. What user-friendly risk prediction tools can be developed based on the results from objectives 1 and 2 which best enable primary, secondary and tertiary care health professionals to obtain future cancer risks?

The primary focus of questions 1 and 2, led by scientists within the Centre for Cancer Genetic Epidemiology, is on the analytical work and the development of the necessary methodologies and technologies for developing breast, ovarian and prostate cancer risk prediction models.

The third workstream aims to develop easy to use tools that implement the risk prediction models from questions 1 and 2 and provide cancer-risk estimates to clinicians at all healthcare levels. This work is carried out jointly with researchers from the Primary Care Unit and the Department of Medical Genetics. We are engaging with stakeholders through workshops and mixed methods research among tertiary, secondary and primary healthcare users. The main objective will be to assess the barriers and facilitators to implementation among each group. We aim to characterize the usability and usefulness of the prototypes across the groups and the development of the tool will be determined through an iterative process of consulting with these clinical investigators.

The CANRISK cancer risk assessment tool is designed to assist clinicians during a consultation with the collection of risk information from patients. This information is used to calculate a cancer risk estimate which will be linked to management recommendations (e.g. screening, preventive medication). The risk prediction will be presented using a range of visual recommendations based on current best evidence from risk communication research.

 

CanRisk 2: Personalising cancer risk prediction for prevention and early detection (2021 – 2026)

Through the CanRisk programme we demonstrated that much more reliable and powerful risk prediction for breast, ovarian and prostate cancer can be achieved by combining data on all genetic, lifestyle and hormonal risk factors for the diseases. We have enabled multifactorial cancer risk-assessment through the CanRisk tool (www.canrisk.org) which allows healthcare professionals to obtain personalised cancer risks easily.

The objective of the CanRisk 2 programme is to enable cancer risk prediction within front-line healthcare, to facilitate the identification and management of at-risk individuals and to promote cancer prevention and early-detection. The programme will address the following specific research questions:

1. What improvement can be achieved in personalised cancer risk prediction that takes advantage of recent discoveries in cancer genomics and epidemiology and that is clinically valid across populations?
2. How can we optimise user-friendly tools to facilitate the use of multifactorial cancer risk prediction in routine clinical practice?
3. How can we operationalise multifactorial cancer risk assessment in primary care and in clinical genetics?

The goals will be achieved through the development of novel cancer risk modelling methods and their application to data from large epidemiological studies to address key challenges in breast, ovarian and prostate cancer risk prediction. These include risk-prediction of cancer subtypes, prediction in individuals of non-European ancestry, prediction of contralateral breast cancer risks and modelling uncertainty in personalised cancer risks. We will incorporate the findings into the CanRisk tool for use by healthcare professionals and develop a new tool for use by patients, enabling them to enter their clinical information into CanRisk prior to their healthcare consultation. We will assess the feasibility, acceptability, the psychological and economic impact of providing multifactorial cancer risk assessment using CanRisk, including polygenic risk scores, in primary care and clinical genetics. We will also use CanRisk to design a new multifactorial cancer risk assessment pathway in clinical genetics and assess the impact through a randomised controlled trial.

The programme aims to take cancer risk stratification to a new, highly personalised level which will allow prevention or screening approaches to be targeted to those most likely to benefit. It will facilitate informed decisions on the timing and type of cancer risk management maximising benefits and minimising harms. Results will be used to design future trials on risk-stratified cancer prevention and early detection approaches, resulting in state-of-the-art models of service delivery for risk-based approaches in routine clinical care.