Cascade screening in HBOC and Lynch syndrome: guidelines and procedures in a UK centre.

Autor: Evans DG; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK. gareth.evans@mft.nhs.uk.; Division of Evolution Infection and Genomic Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, University of Manchester, Manchester, M13 9PL, UK. gareth.evans@mft.nhs.uk., Green K; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK., Burghel GJ; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK., Forde C; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK., Lalloo F; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK., Schlecht H; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK., Woodward ER; Manchester Centre for Genomic Medicine and North-West Genomics Hub, Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK.; Division of Evolution Infection and Genomic Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, University of Manchester, Manchester, M13 9PL, UK.
Jazyk: angličtina
Zdroj: Familial cancer [Fam Cancer] 2024 Jun; Vol. 23 (2), pp. 187-195. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1007/s10689-024-00360-9
Abstrakt: In the 33 years since the first diagnostic cancer predisposition gene (CPG) tests in the Manchester Centre for Genomic Medicine, there has been substantial changes in the identification of index cases and cascade testing for at-risk family members. National guidelines in England and Wales are usually determined from the National Institute of healthcare Evidence and these have impacted on the thresholds for testing BRCA1/2 in Hereditary Breast Ovarian Cancer (HBOC) and in determining that all cases of colorectal and endometrial cancer should undergo screening for Lynch syndrome. Gaps for testing other CPGs relevant to HBOC have been filled by the UK Cancer Genetics Group and CanGene-CanVar project (web ref. https://www.cangene-canvaruk.org/ ). We present time trends (1990-2020) of identification of index cases with germline CPG variants and numbers of subsequent cascade tests, for BRCA1, BRCA2, and the Lynch genes (MLH1, MSH2, MSH6 and PMS2). For BRCA1/2 there was a definite increase in the proportion of index cases with ovarian cancer only and pre-symptomatic index tests both doubling from 16 to 32% and 3.2 to > 8% respectively. A mean of 1.73-1.74 additional family tests were generated for each BRCA1/2 index case within 2 years. Overall close to one positive cascade test was generated per index case resulting in > 1000 risk reducing surgery operations. In Lynch syndrome slightly more cascade tests were performed in the first two years potentially reflecting the increased actionability in males with 42.2% of pre-symptomatic tests in males compared to 25.8% in BRCA1/2 (p < 0.0001).
(© 2024. The Author(s).)
Databáze: MEDLINE
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