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Association betweenBRCA1andBRCA2mutations and cancer phenotype in Spanish breast/ovarian cancer families: Implications for genetic testing

Authors :
Cristina Fernández
Sara Sulleiro
Javier Godino
Miguel de la Hoya
Pedro Pérez-Segura
Ana Osorio
Trinidad Caldés
Eduardo Díaz-Rubio
Javier Benitez
Alicia Tosar
Peter Devilee
Raquel Rodríguez
Source :
International Journal of Cancer. 97:466-471
Publication Year :
2001
Publisher :
Wiley, 2001.

Abstract

Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer, concomitant breast/ovarian cancer in a single patient and prostate cancer but not unilateral breast cancer were associated with BRCA1 and BRCA2 mutations. Male breast cancer was associated with BRCA2 mutations. The presence of male breast cancer was the only cancer phenotype that distinguished BRCA2- from BRCA1-related families. We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics.

Details

ISSN :
00207136
Volume :
97
Database :
OpenAIRE
Journal :
International Journal of Cancer
Accession number :
edsair.doi...........6edf8e6879d581bcc2f0d710045db64e