PMID- 24285840
OWN - NLM
STAT- MEDLINE
DCOM- 20141002
LR  - 20220311
IS  - 1538-7755 (Electronic)
IS  - 1055-9965 (Linking)
VI  - 22
IP  - 12
DP  - 2013 Dec
TI  - Increased rate of phenocopies in all age groups in BRCA1/BRCA2 mutation kindred, 
      but increased prospective breast cancer risk is confined to BRCA2 mutation 
      carriers.
PG  - 2269-76
LID - 10.1158/1055-9965.EPI-13-0316-T [doi]
AB  - BACKGROUND: To establish, if among unaffected noncarrier relatives in a family 
      with an established BRCA1/2 mutation, there is an increased risk of breast 
      cancer. METHODS: We identified 49 women with breast cancer who were first-degree 
      relatives of a pathogenic mutation carrier among 807 BRCA1/2 families but who 
      tested negative for the specific mutation. A prospective analysis of breast 
      cancer from date of family ascertainment was performed for first-degree relatives 
      of proven BRCA1/2 mutation carriers and compared with population-expected 
      incidence rates. RESULTS: Women who prospectively test negative for BRCA1/2 
      mutations showed excess risk of breast cancer to be confined to BRCA2 noncarriers 
      with an observed:expected (O/E) ratio of 4.57 [95% confidence interval (CI) 
      2.50-7.67; P < 0.0001; O/E in BRCA1 noncarriers, 1.77]; this dropped to 2.01 for 
      BRCA2 [relative risk (RR), 1.99; 95% CI, 0.54-5.10] from date of predictive test. 
      Genotyping of 18 breast cancer susceptibility single-nucleotide polymorphisms 
      (SNP) defined an RR of 1.31 for BRCA2 breast cancer phenocopies with a breast 
      cancer diagnosis at age less than 60 years. CONCLUSION: Noncarriers remain at 
      risk in the prospective follow-up of women who tested negative for BRCA1/2. Women 
      testing negative in BRCA2 families may have increased risk of breast cancer 
      compared with population levels, particularly with strong breast cancer history 
      in close relatives. Any increased risk in BRCA1 families is likely to be 
      insufficient to recommend additional interventions. IMPACT: Our work can help 
      with counseling women from BRCA1/2 families who have tested negative, and could 
      impact on how individual breast cancer risk is related back to these women.
CI  - (c)2013 AACR.
FAU - Evans, D Gareth R
AU  - Evans DG
AD  - Authors' Affiliations: Department of Genetic Medicine, The University of 
      Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital; 
      Genesis Prevention Centre, University Hospital of South Manchester Southmoor 
      Road; Centre for Health Informatics, Institute of Population Health, The 
      University of Manchester, Manchester; and Centre for Rare Diseases and 
      Personalised Medicine, School of Clinical and Experimental Medicine, University 
      of Birmingham College of Medical and Dental Sciences, and West Midlands Regional 
      Genetics Service, Birmingham, United Kingdom.
FAU - Ingham, Sarah L
AU  - Ingham SL
FAU - Buchan, Iain
AU  - Buchan I
FAU - Woodward, Emma R
AU  - Woodward ER
FAU - Byers, Helen
AU  - Byers H
FAU - Howell, Anthony
AU  - Howell A
FAU - Maher, Eamonn R
AU  - Maher ER
FAU - Newman, William G
AU  - Newman WG
FAU - Lalloo, Fiona
AU  - Lalloo F
LA  - eng
GR  - DHCS/06/06/013/DH_/Department of Health/United Kingdom
GR  - MC_PC_13042/MRC_/Medical Research Council/United Kingdom
GR  - MR/K006665/1/MRC_/Medical Research Council/United Kingdom
GR  - RP-PG-0707-10031/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131127
PL  - United States
TA  - Cancer Epidemiol Biomarkers Prev
JT  - Cancer epidemiology, biomarkers & prevention : a publication of the American 
      Association for Cancer Research, cosponsored by the American Society of 
      Preventive Oncology
JID - 9200608
SB  - IM
MH  - Breast Neoplasms/*genetics
MH  - Female
MH  - *Genes, BRCA1
MH  - *Genes, BRCA2
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - *Mutation
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Risk Factors
EDAT- 2013/11/29 06:00
MHDA- 2014/10/03 06:00
CRDT- 2013/11/29 06:00
PHST- 2013/11/29 06:00 [entrez]
PHST- 2013/11/29 06:00 [pubmed]
PHST- 2014/10/03 06:00 [medline]
AID - 1055-9965.EPI-13-0316-T [pii]
AID - 10.1158/1055-9965.EPI-13-0316-T [doi]
PST - ppublish
SO  - Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2269-76. doi: 
      10.1158/1055-9965.EPI-13-0316-T. Epub 2013 Nov 27.