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.

  title={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.},
  author={Antonis C. Antoniou and Paul D. P. Pharoah and Steven A. Narod and Harvey A. Risch and Jorunn Erla Eyfjord and John L. Hopper and Niklas Loman and Hakan L. Olsson and Oskar Thor Johannsson and {\AA}ke Borg and Barbara Pasini and Paolo Radice and Siranoush Manoukian and Diana M. Eccles and Na Tang and Edith Ol{\'a}h and Hoda Anton-Culver and Ellen Warner and Jan Lubiński and Jacek Gronwald and Bohdan G{\'o}rski and Hrafn Tulinius and Steinunn Thorlacius and Hannaleena Eerola and Heli Nevanlinna and Kirsi Syrj{\"a}koski and Olli Kallioniemi and D.J. Thompson and Chris Evans and Julian Peto and Fiona Lalloo and D. Gareth R. Evans and Douglas F. Easton},
  journal={American journal of human genetics},
  volume={72 5},
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… 
Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations
BRCA1 mutation carriers conferred lower overall breast and ovarian cancer risks than reported so far, while the estimates of BRCA2 mutations were among the lowest.
Large genomic rearrangements in the familial breast and ovarian cancer gene BRCA1 are associated with an increased frequency of high risk features
If validated, large genomic rearrangements could be included in cancer risk prediction tools to improve personalised cancer risk Prediction estimates and may guide cost-minimising mutation screening strategies in some healthcare settings.
The Average Cumulative Risks of Breast and Ovarian Cancer for Carriers of Mutations in BRCA1 and BRCA2 Attending Genetic Counseling Units in Spain
The results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCa2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations.
Breast and ovarian cancer risk evaluation in families with a disease-causing mutation in BRCA1/2
The penetrance, the earlier onset of the disease and the effect of mutations on the risk of developing breast and ovarian cancer were evaluated in 344 females belonging to 34 families from the Basque Country in Spain.
Cancer risks in first degree relatives of BRCA1 mutation carriers: effects of mutation and proband disease status
The risk of breast cancer in female relatives of women with a BRCA1 mutation depends on whether the proband was diagnosed with breast or ovarian cancer.
Association between family history, mutation locations, and prevalence of BRCA1 or 2 mutations in ovarian cancer patients
The rate of germline BRCA1 or 2 mutations in ovarian cancer patients without a family history or breast or ovarian cancer is low, however, in women with additional family members affected, the prevalence is considerably higher than previously reported.
Estimating risk of breast cancer in carriers of BRCA1 and BRCA2 mutations: a meta‐analytic approach
A combined estimator of penetrance from combined estimates of the prevalence of BRCA mutations in women with and without breast cancer and from the probability of breast cancer by using Bayes' Theorem is proposed.
BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models.
The results suggest that HBC families, the largest pool in this series, represent an heterogeneous group where the apparently faulty performances of the prediction models might be at least partially explained by the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements) or by mutations on different breast cancer related genes.


Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study.
  • J. Hopper, M. Southey, D. Venter
  • Biology, Medicine
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 1999
Testing for protein-truncating mutations in exons 2, 11, and 20 of BRCA1 and exons 10 and 11 of B RCA2 was conducted in a population-based sample of 388 Australian women with breast cancer diagnosed before age 40, finding no change in risk.
Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases
  • P. Pharoah
  • Medicine, Biology
    British Journal of Cancer
  • 2000
Mutation prevalence was substantially higher in cases diagnosed before 35 years-of-age and with increasing number of relatives affected with breast or ovarian cancer, however, most mutation carriers were diagnosed in the older age groups, and a minority reported a first-degree relative with breast cancer.
Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer.
Almost half (48%) of women in southern Sweden with early-onset breast cancer have some family history of breast or ovarian cancer, and 9.0% of early-onset breast cancer cases are associated with a germline mutation in BRCA1 or BRCa2.
Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.
Data from families with evidence of linkage to BRCA1 is used to estimate the age-specific risks of breast and ovarian cancer in BRCa1-mutation carriers and to examine the variation in risk between and within families.
Risk models for familial ovarian and breast cancer
BRCA1 and BRCA2 may be sufficient to explain the majority of familial ovarian cancer and that families without mutations can be explained by sensitivity of mutation testing and chance clusters of sporadic cases.
Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.
The hypothesis that pathways involving endocrine signaling, as measured through AIB1 genotype and reproductive history, may have a substantial effect on BRCA1/2-associated breast cancer risk is supported.
Risks of cancer in BRCA1-mutation carriers
Population-based study of risk of breast cancer in carriers of BRCA2 mutation
Cancer Incidence in BRCA1 mutation carriers.
In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men.
BRCA1 and BRCA2 mutations in a population-based study of male breast cancer
The data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found.