Using tumour pathology to identify people at high genetic risk of breast and colorectal cancers

J. L. Hopper, M. A. Jenkins, James G Dowty, Gillian S Dite, Carmel Apicella, Louise Keogh, Aung K Win, J. P. Young, D. Buchanan, M. D. Walsh, Christophe Rosty, Laura Baglietto, Gianluca Severi, K. A. Phillips, E. M. Wong, A. Dobrovic, Paul Waring, Ingrid Winship, Susan J Ramus, G. G. GilesM. C. Southey

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


Genes have been identified for which germline mutations are associatedwith highlifetimerisks of breast,colorectalandother cancers. Identification of mutation carriers through genetic testing is important as it could help lower cancer incidence and mortality. The translation of genetic information into better health outcomes is expensive because of the costs of genetic counselling as well as laboratory testing. Approaches to triage for mutation screening of known genes which rely on cancer family history are not necessarily sensitive and specific or the most cost-effective. Recent population-based research has shown that the cancers and precancerous lesions arising in mutation carriers have specific molecular and morphological characteristics. People with colorectal cancer, especially those diagnosedat ayoungage,whosetumours exhibit microsatellite instabilityandsomespecific pathologyandimmunohistochemically- defined features are more likely to carry a germline mutation in one of four mismatch repair genes. Some morphological and immunohistochemically-defined features are associated with breast cancers arising in women who carry BRCA1 or BRCA2 germline mutations, especially if at a young age. Screening paradigms based on molecular and morphological features that predict mutation status, especially if focused on early-onset disease, have the potential to identify mutation carriers with greater sensitivityand specificity, and in a more cost-effective way, than those based on family history alone. Genetic testing results could help inform treatment if those affected are tested soon after diagnosis using pathologyled selection strategies to identify cases most likely to carry germline mutations.We propose how this new approach could be undertaken by having genetic testing and counselling prioritised to those with the greatest probability of carrying a germlinemutation in these knowncancer predispositiongenes.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
Issue number2
Publication statusPublished - Feb 2012
Externally publishedYes


  • BRCA1
  • BRCA2
  • Breast cancer
  • Colorectal cancer
  • DNA mismatch repair genes
  • Genetic risk
  • Mutation carriers
  • Statistics
  • Tumour pathology
  • Tumourmorphology

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