Population genetic testing for cancer susceptibility: founder mutations to genomes.
The current standard model for identifying carriers of high-risk mutations in cancer-susceptibility genes (CSGs) generally involves a process that is not amenable to population-based testing: access to genetic tests is typically regulated by health-care providers on the basis of a labour-intensive assessment of an individual's personal and family history of cancer, with face-to-face genetic counselling performed before mutation testing. Several studies have shown that application of these selection criteria results in a substantial proportion of mutation carriers being missed. Population-based genetic testing has been proposed as an alternative approach to determining cancer susceptibility, and aims for a more-comprehensive detection of mutation carriers. Herein, we review the existing data on population-based genetic testing, and consider some of the barriers, pitfalls, and challenges related to the possible expansion of this approach. We consider mechanisms by which population-based genetic testing for cancer susceptibility could be delivered, and suggest how such genetic testing might be integrated into existing and emerging health-care structures. The existing models of genetic testing (including issues relating to informed consent) will very likely require considerable alteration if the potential benefits of population-based genetic testing are to be fully realized.
Department of Human Genetics, McGill University, 1205 Docteur-Penfield, Montreal, QC H3A 1B1, Canada.|Department of Medicine and Oncology, McGill University, 1205 Docteur-Penfield, Montreal, QC H3A 1B1, Canada.
William D
WD
Foulkes
Department of Human Genetics, McGill University, 1205 Docteur-Penfield, Montreal, QC H3A 1B1, Canada.|Centre of Genomics and Policy, Genome Quebec Innovation Centre, McGill University, 1205 Docteur-Penfield, Montreal, QC H3A 1B1, Canada.
Bartha Maria
BM
Knoppers
Genomics England 100,000 Genomes Project, William Harvey Research Institute, Barts and The London, Queen Mary University, Charterhouse Square, London EC1M 6BQ, UK.|Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
Clare
C
Turnbull
D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D008403:Mass Screening; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D018570:Risk Assessment; D017422:Sequence Analysis, DNA / Q000379:methods
D014408:Biomarkers, Tumor