Document Detail

Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.
MedLine Citation:
PMID:  12677558     Owner:  NLM     Status:  MEDLINE    
Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.
A Antoniou; P D P Pharoah; S Narod; H A Risch; J E Eyfjord; J L Hopper; N Loman; H Olsson; O Johannsson; A Borg; B Pasini; P Radice; S Manoukian; D M Eccles; N Tang; E Olah; H Anton-Culver; E Warner; J Lubinski; J Gronwald; B Gorski; H Tulinius; S Thorlacius; H Eerola; H Nevanlinna; K Syrjäkoski; O-P Kallioniemi; D Thompson; C Evans; J Peto; F Lalloo; D G Evans; D F Easton
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-04-03
Journal Detail:
Title:  American journal of human genetics     Volume:  72     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-21     Completed Date:  2003-07-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1117-30     Citation Subset:  IM    
Cancer Research U.K. Genetic Epidemiology Unit, Department of Public Health, University of Cambridge, Cambridge, United Kingdom.
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MeSH Terms
Age Distribution
Breast Neoplasms / epidemiology,  genetics*
Cohort Studies
Genes, BRCA1*
Genes, BRCA2*
Genetic Testing / statistics & numerical data
Middle Aged
Ovarian Neoplasms / epidemiology,  genetics*
Risk Assessment
World Health
Grant Support
Erratum In:
Am J Hum Genet. 2003 Sep;73(3):709

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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