The CanRisk Research Programme is a CRUK funded research programme. Its overarching objective is to enable cancer risk prediction within routine front-line healthcare, to facilitate the identification and management of at-risk individuals and to promote cancer prevention and early-detection.
To achieve this objective, the programme addresses three key research questions:
- 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?
- How can we optimise user-friendly tools to facilitate the use of personalised, multifactorial cancer risk prediction in routine clinical practice?
- How can we operationalise multifactorial cancer risk assessment in primary care and in clinical genetics?
These questions are addressed through five interconnected workstreams:
- Workstream 1: Cancer risk model development and evaluation
- Workstream 2: Personalising cancer risk assessment for BRCA1 and BRCA2 carriers
- Workstream 3: CanRisk tool development and evaluation
- Workstream 4: Operationalising CanRisk for use in Primary Care
- Workstream 5: Operationalising CanRisk in NHS cancer genetics clinics
Workstream 1
Workstream 1 focuses on leveraging the latest advances in genetics and epidemiology to improve cancer risk prediction models for breast cancer, epithelial ovarian cancer, prostate cancer, and other cancers. This workstream aims to address key challenges in cancer risk prediction by developing and refining models that deliver greater accuracy and applicability across diverse populations and cancer types.
A major objective is to customise the models for women and men of non-European ancestry. The workstream will also integrate new susceptibility genes, updated polygenic risk scores, mutation-specific risks, and automated methods for mammographic density measurement into the CanRisk platform.
Furthermore, the uncertainty in predicted cancer risks will be estimated and incorporated into the models to enhance their clinical relevance. Finally, the performance of these updated models will be rigorously evaluated using independent prospective cohort studies, ensuring the models provide clinically valid risks.
Workstream 2
Workstream 2 aims to enhance personalised cancer risk prediction for women and men with pathogenic variants in the BRCA1 and BRCA2 genes. The goal is to provide more tailored risk assessments by incorporating genetic, lifestyle, and hormonal factors into predictive models.
A key focus of this workstream is to understand the variability in cancer risks associated with BRCA1 and BRCA2 mutations. This includes examining how genetic profiles, lifestyle factors, hormonal influences, and specific mutation characteristics contribute to differences in risk. The insights gained will be integrated into the multifactorial cancer risk prediction models for breast cancer, epithelial ovarian cancer, and prostate cancer developed in Workstream 1. These customised BRCA1 and BRCA2 components will then be incorporated into the CanRisk platform to improve accuracy and applicability.
Additionally, this workstream aims to define the long-term health consequences of carrying BRCA1 and BRCA2 mutations. This includes investigating the risks of cancers beyond breast and ovarian cancer, the likelihood of developing second cancers, and the impact of these mutations on mortality and morbidity from non-malignant diseases.
Workstream 3
Workstream 3 focuses on developing the CanRisk platform by optimising patient data collection processes and incorporating novel risk prediction features developed in workstreams 1 and 2. A key objective is to develop a user-friendly data collection tool that allows patients to self-complete essential parts of CanRisk prior to their consultations with healthcare professionals. This tool will streamline data collection, reducing the burden on healthcare professionals and improving efficiency.
Furthermore, CanRisk will incorporate a Prostate Cancer risk model, enabling healthcare professionals to obtain prostate cancer risk assessments through the same interface used for breast and epithelial ovarian cancer risk predictions.
Workstream 4
Workstream 4 aims to integrate multifactorial cancer risk assessment into routine primary care practice, focusing on the proactive use of CanRisk. To achieve these objectives, the team will develop a comprehensive training package for primary care healthcare professionals, equipping them to conduct multifactorial cancer risk assessments that incorporate polygenic risk factors. Then, the team will evaluate the feasibility and acceptability of proactively offering CanRisk in primary care settings, using breast cancer as an exemplar. This includes assessing the perspectives of both healthcare professionals and patients, quantifying the uptake of proactive breast cancer risk assessments, and evaluating the psychological and behavioural impacts on women who undergo these assessments.
Workstream 5
Workstream 5 will develop a new pathway which uses CanRisk multifactorial risk-assessment to allow precision targeted cancer surveillance for unaffected women referred to genetics clinics with cancer family history. This pathway is designed with existing service structures in mind to facilitate the smooth and rapid operationalisation of CanRisk across NHS cancer genetics clinics.
To achieve this objective, a randomised controlled study will be conducted to assess the clinical, psycho-social and economic impact of conducting upfront multifactorial risk assessment in unaffected women referred to genetics clinics.
Investigators:
Principal Investigator: Antonis Antoniou
Co-Investigators: Douglas Easton, Stephanie Archer, Juliet Usher-Smith, Marc Tischkowitz, Fiona Walter, Stephen Morris
Programme Manager: Adam Stokes