Abstract
We have designed the user-friendly COS software with the intent to improve estimation of the probability of a family carrying a deleterious BRCA gene mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO software, but it incorporates improved assumptions on cancer incidence in women with and without a deleterious mutation, takes into account relatives up to the fourth degree and allows researchers to consider an hypothetical third gene or a polygenic model of inheritance. Since breast cancer incidence and penetrance increase over generations, we estimated birth-cohort-specific incidence and penetrance curves. We estimated breast and ovarian cancer penetrance in 384 BRCA1 and 229 BRCA2 mutated families. We tested the COS performance in 436 Italian breast/ovarian cancer families including 79 with BRCA1 and 27 with BRCA2 mutations. The area under receiver operator curve (AUROC) was 84.4 %. The best probability threshold for offering the test was 22.9 %, with sensitivity 80.2 % and specificity 80.3 %. Notwithstanding very different assumptions, COS results were similar to BRCAPRO v6.0.
Original language | English |
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Pages (from-to) | 117-128 |
Number of pages | 12 |
Journal | Familial Cancer |
Volume | 14 |
Issue number | 1 |
DOIs | |
Publication status | Published - Nov 6 2014 |
Keywords
- BRCA genes
- Breast cancer
- Mutation probability
- Ovarian cancer
- Penetrance
- Risk estimation model
ASJC Scopus subject areas
- Cancer Research
- Genetics
- Oncology
- Genetics(clinical)
- Medicine(all)