Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations

被引：0
作者：
Fabio Marroni
Paolo Aretini
Emma D'Andrea
Maria Adelaide Caligo
Laura Cortesi
Alessandra Viel
Enrico Ricevuto
Marco Montagna
Giovanna Cipollini
Massimo Federico
Manuela Santarosa
Paolo Marchetti
Joan E Bailey-Wilson
Generoso Bevilacqua
Giovanni Parmigiani
Silvano Presciuttini
机构：
[1] Transplants and New Technologies in Medicine,Department of Oncology
[2] Section of Pathology,Department of Oncology and Surgical Sciences
[3] University of Pisa,Department of Oncology and Hematology
[4] Center of Statistical Genetics,Department of Experimental Medicine
[5] University of Pisa,Departments of Oncology and Biostatistics
[6] Section of Oncology,undefined
[7] Section of Viral and Molecular Oncology,undefined
[8] University of Padua,undefined
[9] University of Modena and Reggio Emilia,undefined
[10] Experimental Oncology 1,undefined
[11] Oncology Referral Center,undefined
[12] IRCCS,undefined
[13] University of L'Aquila,undefined
[14] IST,undefined
[15] Section of Viral and Molecular Oncology,undefined
[16] University of Padua,undefined
[17] Modena's Oncology Center,undefined
[18] University of Modena and Reggio Emilia,undefined
[19] Inherited Disease Research Branch,undefined
[20] National Human Genome Research Institute,undefined
[21] National Institutes of Health,undefined
[22] Johns Hopkins University,undefined
来源：
European Journal of Human Genetics | 2004年 / 12卷
关键词：
BRCA1; BRCA2; penetrance; genetic testing; predictive models; BRCAPRO;
D O I：
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中图分类号：
学科分类号：
摘要：
Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20–34%) at age 50 years and 39% (27–52%) at age 70 in BRCA1 carriers, and 26% (0.18–0.34%) at age 50 and 44% (29–58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7–22%) at age 50 and 43% (21–66%) at age 70 in BRCA1 carriers and 3% (0–7%) at age 50 and 15% (4–26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates.
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页码：899 / 906
页数：7
相关论文
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