Half of germline pathogenic and likely pathogenic variants found on panel tests do not fulfil NHS testing criteria.
Abstract
Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and testing has been restricted by eligibility criteria. As the cost of sequencing decreases, the question of expanding multi-gene cancer panels to a broader population arises. We evaluated how many additional actionable genetic variants are returned by unrestricted panel testing in the private sector compared to those which would be returned by adhering to current NHS eligibility criteria. We reviewed 152 patients referred for multi-gene cancer panels in the private sector between 2014 and 2016. Genetic counselling and disclosure of all results was standard of care provided by the Consultant. Every panel conducted was compared to current eligibility criteria. A germline pathogenic / likely pathogenic variant (P/LP), in a gene relevant to the personal or family history of cancer, was detected in 15 patients (detection rate of 10%). 46.7% of those found to have the P/LP variants (7 of 15), or 4.6% of the entire set (7 of 152), did not fulfil NHS eligibility criteria. 46.7% of P/LP variants in this study would have been missed by national testing guidelines, all of which were actionable. However, patients who do not fulfil eligibility criteria have a higher Variant of Uncertain Significance (VUS) burden. We demonstrated that the current England NHS threshold for genetic testing is missing pathogenic variants which would alter management in 4.6%, nearly 1 in 20 individuals. However, the clinical service burden that would ensue is a detection of VUS of 34%.
Collections
Subject
Humans
Neoplasms
Genetic Predisposition to Disease
Incidence
Risk Assessment
Retrospective Studies
Genetic Counseling
Germ-Line Mutation
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
State Medicine
England
Female
Male
Young Adult
Genetic Testing
Biomarkers, Tumor
Research team
Oncogenetics
Language
eng
Date accepted
2022-01-20
License start date
2022-02-21
Citation
Scientific reports, 2022, 12 (1), pp. 2507 - ?
Publisher
NATURE PORTFOLIO