CanGeneCanVar

There is currently a knowledge gap between laboratory discovery of cancer predisposition genes, and implementation of best-practice clinical care for people and families with harmful variants in these genes. CGCV is a translational research programme that is generating the evidence base, infrastructure and resources to bridge this gap and improve outcomes for patients and families with hereditary cancer syndromes.

The overall aim of CGCV is to generate evidence of the risks relating to cancer susceptibility genes, and effectiveness of clinical interventions in different populations, to inform clinical decision-making.

CGCV consists of six interrelated work packages:

1. Data collection, harmonisation, linkage, and sharing.
2. Generation of laboratory resources to facilitate understanding and interpretation of genetic variants.
3. Development and dissemination of evidence-based, best practice clinical care guidelines.
4. Development of tools to support patients in their decision making.
5. Education of the wider NHS workforce.
6. Ethics and governance.

NDRS are leading on Work Package 1 (WP1), described by CGCV's independent Scientific Advisory Committee as 'the core of the entire project and the one work programme with potentially practice-changing implication for the NHS'. WP1 is built upon NDRS's collection, standardisation and amalgamation of genetic testing data from across NHS laboratories.

Together with colleagues from Health Data Insight (HDI), CRUK, The Institute of Cancer Research (ICR) and the University of Oxford, NDRS are building an end-to-end programme including restructuring heterogeneous data to a common data model, provision of a platform for data sharing with the clinical community, and analytical support and domain expertise for early use cases of the germline genetic data.

The partnership has delivered the following outputs:

• Loong L, Huntley C, McRonald F, et al. Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996-2020: development of a national resource of patient-level genomics laboratory records. J Med Genet. 2023;60(7):669-678. doi:10.1136/jmg-2022-108800

• Huntley C, Loong L, Mallinson C, et al. The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource. EClinicalMedicine. 2024 Feb 7;69:102465. doi: 10.1016/j.eclinm.2024.102465.
• Allen S, Loong L, Garrett A, et al. Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant datahttps://jmg.bmj.com/content/61/4/305.long: findings from CanVIG-UK national molecular laboratory survey. J Med Genet. 2024 Mar 21;61(4):305-312.
• Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study - The Lancet Regional Health – Europe
• Loong L, Huntley C, Pethick J, et al. Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study. J Med Genet. 2024 Nov 25;61(12):1080-1088. doi: 10.1136/jmg-2024-110231.
• Allen I, Hassan H, Walburga Y, et al. Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers. J Clin Oncol. 2025 Feb 20;43(6):651-661. doi: 10.1200/JCO.24.01146. Epub 2024 Oct 29. PMID: 39475295; PMCID: PMC7616773.
• Hassan H, Rahman T, Bacon A et al. Long-term outcomes of bilateral salpingo-oophorectomy in women with personal history of breast cancer: BMJ Oncology 2025;4:e000574.
• Hassan H, Allen I, Rahman T, et al. Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records. The Lancet Oncology. In press, 2025.

You can find out more about the entire work programme by visiting the CanGene-CanVar website.