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

Hopper, J. L., Jenkins, M. A., Dowty, J. G., Dite, G. S., Apicella, C., Keogh, L., Win, A. K., Young, J. P., Buchanan, D., Walsh, M. D., Rosty, C., Baglietto, L., Severi, G., Phillips, K. A., Wong, E. M., Dobrovic, A., Waring, P., Winship, I., Ramus, S. J., Giles, G. G. and Southey, M. C. (2012) Using tumour pathology to identify people at high genetic risk of breast and colorectal cancers. Pathology, 44 2: 89-98. doi:10.1097/PAT.0b013e32834e8e5b

Author Hopper, J. L.
Jenkins, M. A.
Dowty, J. G.
Dite, G. S.
Apicella, C.
Keogh, L.
Win, A. K.
Young, J. P.
Buchanan, D.
Walsh, M. D.
Rosty, C.
Baglietto, L.
Severi, G.
Phillips, K. A.
Wong, E. M.
Dobrovic, A.
Waring, P.
Winship, I.
Ramus, S. J.
Giles, G. G.
Southey, M. C.
Title Using tumour pathology to identify people at high genetic risk of breast and colorectal cancers
Journal name Pathology   Check publisher's open access policy
ISSN 0031-3025
Publication date 2012-02
Sub-type Article (original research)
DOI 10.1097/PAT.0b013e32834e8e5b
Open Access Status
Volume 44
Issue 2
Start page 89
End page 98
Total pages 10
Place of publication London, United Kingdom
Publisher Lippincott Williams & Wilkins
Collection year 2013
Language eng
Formatted abstract
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.
Keyword BRCA1
Breast cancer
Colorectal cancer
DNA mismatch repair genes
Genetic risk
Mutation carriers
Tumour morphology
Tumour pathology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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