Abstract
The true prevalence of BRCA1/BRCA2 (BRCAs) germline mutations in sporadic breast or ovarian cancer (SBC/SOC) in Caucasian population is not well established. The aim of the study is to establish the prevalence of BRCAs mutations in SBC to ponder its relevance in the programs of genetic counseling in cancer and to explore the genotype-phenotype relationship of these particular breast cancers. The study was performed in 495 SBC. We sought 46 BRCA1 and 53 BRCA2 pathogenic mutations reported in the Spanish population. We followed a high resolution melting method performed in the LightCycler 480 (Roche Diagnostics) for the screening of these Spanish mutations using 49 primer pairs. Eight different deleterious mutations, one of them novel, were detected in nine patients, five without family history of BC/OC, what yields a true prevalence of 1.05% for BRCAs mutations in SBC. Furthermore, we found 18 unknown variants. Larger tumour size (T > 1) and earlier presentation are the independent parameters associated with the presence of BRCAs pathogenic mutations in SBC (P < 0.01) and the BRCA1 mutations carriers develop steroid—receptors negative tumors. Our results indicate that the true prevalence of BRCAs germline deleterious mutations in SBC of Spaniards is low. However, this does not lessens its relevance since the presence of BRCAs mutations in SBC could represent circa 16% of total BRCAs mutations detected in BC. SBCs of BRCAs mutation carriers have phenotype more aggressiveness than SBC without BRCAs mutation.
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Abbreviations
- BC:
-
Breast cancer
- OC:
-
Ovarian cancer
- BRCAs :
-
BRCA1 and BRCA2
- SBC:
-
Sporadic breast cancer
- PGCCVC:
-
Program of genetic counseling in cancer of the Valencian community
- HRM:
-
High resolution melting
- UVs:
-
Unknown variants
- ESE:
-
Exonic splicing enhancers
- PESRs:
-
Putative exonic splicing regulatory elements
- SRE:
-
Splicing regulatory elements
- SR:
-
Serine/arginine rich
- SPSS:
-
Statistical program for social sciences
- T:
-
Tuomur size
- ER:
-
Estrogen receptor
- PR:
-
Progesterone receptor
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Acknowledgments
This work has been funded by the grants FIS PI060505 (Instituto de Salud Carlos III) and AP-042/07 (Consellería de Sanitat). We should thank the help and support given by the “Oficina del Plan del Cáncer. Dirección General de Salud Pública”. Consellería de Sanitat. Comunidad Valenciana. We thank the help and support given by “Instituto de Investigación Sanitaria del Hospital La Fe” and “Fundación de Investigación de la Asociación Española contra el Cáncer” since they have funded the contract to Inmaculada Juan (Specialist in Clinical Analysis) in cancer research, enabled her participation in this study. We are grateful to Dr. Vicente Guillén Ponce for his collaboration in providing patient samples for this study.
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de Juan Jiménez, I., Esteban Cardeñosa, E., Palanca Suela, S. et al. Low prevalence of BRCA1 and BRCA2 mutations in the sporadic breast cancer of Spanish population. Familial Cancer 11, 49–56 (2012). https://doi.org/10.1007/s10689-011-9481-7
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DOI: https://doi.org/10.1007/s10689-011-9481-7