J Med Genet

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
[Advanced]

Published Online First: 1 November 2006. doi:10.1136/jmg.2006.043091
Journal of Medical Genetics 2007;44:10-15
Copyright © 2007 by the BMJ Publishing Group Ltd.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow web only appendix
Right arrow All Versions of this Article:
jmg.2006.043091v1
44/1/10    most recent
Right arrow Submit a response
Right arrow Read responses to this article
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smith, A
Right arrow Articles by Evans, D G R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, A
Right arrow Articles by Evans, D G R
Right arrowPubmed/NCBI databases
*OMIM
Medline Plus Health Information
*Breast Cancer
*Genetic Testing
*Ovarian Cancer
*Genetics Home Reference

ORIGINAL ARTICLE

Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening

A Smith1, A Moran2, M C Boyd1, M Bulman1, A Shenton1, L Smith3, R Iddenden2, E R Woodward3, F Lalloo1, E R Maher3, D G R Evans1

1 Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Manchester, UK
2 North Western Cancer Registry, Center for Cancer Epidemiology, Christie Hospital, Manchester
3 Section of Medical and Molecular Genetics, University of Birmingham School of Medicine; West Midlands Regional Genetics Service, Birmingham, UK

Correspondence to:
D G R Evans
University Department of Medical Genetics and Regional Genetic Service, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK; gareth.evans{at}cmmc.nhs.uk] Background: The identification of BRCA1 and BRCA2 mutations in familial breast cancer kindreds allows genetic testing of at-risk relatives. Those who test negative are usually reassured and additional breast cancer surveillance is discontinued. However, we postulated that in high-risk families, such as those seen in clinical genetics centres, the risk of breast cancer might be influenced not only by the BRCA1/BRCA2 mutation but also by modifier genes. One manifestation of this would be the presence of phenocopies in BRCA1/BRCA2 kindreds.

Methods: 277 families with pathogenic BRCA1/BRCA2 mutations were reviewed and 28 breast cancer phenocopies identified. The relative risk of breast cancer in those testing negative was assessed using incidence rates from our cancer registry based on local population.

Results: Phenocopies constituted up to 24% of tests on women with breast cancer after the identification of the mutation in the proband. The standardised incidence ratio for women who tested negative for the BRCA1/BRCA2 family mutation was 5.3 for all relatives, 5.0 for all first-degree relatives (FDRs) and 3.2 (95% confidence interval 2.0 to 4.9) for FDRs in whose family all other cases of breast and ovarian cancer could be explained by the identified mutation. 13 of 107 (12.1%) FDRs with breast cancer and no unexplained family history tested negative.

Conclusion: In high-risk families, women who test negative for the familial BRCA1/BRCA2 mutation have an increased risk of breast cancer consistent with genetic modifiers. In light of this, such women should still be considered for continued surveillance.


Abbreviations: FDR, first-degree relative; NICE, National Institute for Clinical Excellence; SIR, standardised incidence ratio




This article has been cited by other articles:


Home page
J. Mol. Diagn.Home page
D. C. Allain
Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology
J. Mol. Diagn., September 1, 2008; 10(5): 383 - 395.
[Abstract] [Full Text] [PDF]


Home page
The Obstetrician and GynaecologistHome page
L. A Devlin and P. J Morrison
Inherited gynaecological cancer syndromes
Obstet Gynaecol (Lond), January 1, 2008; 10(1): 9 - 15.
[Abstract] [Full Text] [PDF]


Home page
Ann. Surg. Oncol.Home page
M. Fatouros, G. Baltoyiannis, and D. H. Roukos
The Predominant Role of Surgery in the Prevention and New Trends in the Surgical Treatment of Women With BRCA1/2 Mutations
Ann. Surg. Oncol., January 1, 2008; 15(1): 21 - 33.
[Abstract] [Full Text] [PDF]


Home page
J. Med. Genet.Home page
D. Goldgar, V. Venne, T. Conner, and S. Buys
BRCA phenocopies or ascertainment bias?
J. Med. Genet., August 1, 2007; 44(8): e86 - e86.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
F. Eisinger
Phenocopies: actual risk or self-fulfilling prophecy?
J. Med. Genet., August 1, 2007; 44(8): e87 - e87.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
A Smith, M C Boyd, M Bulman, A Shenton, F Lalloo, D G R Evans, A Moran, R Iddenden, L Smith, E R Woodward, et al.
Response to correspondence on "Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening"
J. Med. Genet., August 1, 2007; 44(8): e88 - e88.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
E. Rowan, A. Poll, and S. A Narod
A prospective study of breast cancer risk in relatives of BRCA1/BRCA2 mutation carriers
J. Med. Genet., August 1, 2007; 44(8): e89 - e89.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
P Sasieni
Phenocopies in families seen by cancer geneticists
J. Med. Genet., June 1, 2007; 44(6): e82 - e82.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
M M A Tilanus-Linthorst
No screening yet after a negative test for the family mutation
J. Med. Genet., May 1, 2007; 44(5): e79 - e79.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
J. Gronwald, C. Cybulski, J. Lubinski, and S. A Narod
Phenocopies in breast cancer 1 (BRCA1) families: implications for genetic counselling
J. Med. Genet., April 1, 2007; 44(4): e76 - e76.
[Full Text] [PDF]

eLetters:

Read all eLetters

No screening yet after a negative test for the family mutation
Madeleine M Tilanus-Linthorst
J Med Genet, 20 Dec 2006 [Full text]
BRCA Phenocopies or Ascertainment Bias?
David E Goldgar, et al.
J Med Genet, 5 Mar 2007 [Full text]
Phenocopies: actual risk or self-fulfilling prophecy?
Francois Eisinger
J Med Genet, 19 Mar 2007 [Full text]
Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening
D Gareth Evans, et al.
J Med Genet, 15 May 2007 [Full text]



HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 2007 by the BMJ Publishing Group Ltd.