Population genetic testing for cancer susceptibility: founder mutations to genomes

Nat Rev Clin Oncol. 2016 Jan;13(1):41-54. doi: 10.1038/nrclinonc.2015.173. Epub 2015 Oct 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / genetics
  • Female
  • Founder Effect*
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Genome, Human*
  • Humans
  • Mass Screening
  • Mutation*
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Ovarian Neoplasms / genetics
  • Risk Assessment
  • Sequence Analysis, DNA / methods


  • Biomarkers, Tumor