Mutations and polymorphic BRCA variants transmission in breast cancer familial members

Brunella Pilato, Marianna Martinucci, Katia Danza, Rosamaria Pinto, Daniela Petriella, Rosanna Lacalamita, Michele Bruno, Rossana Lambo, Cosimo D'Amico, Angelo Paradiso, Stefania Tommasi

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We previously showed that about 80% of breast cancer patients at high risk to carry mutation in BRCA genes presented at least one polymorphism in these genes which resulted potentially harmful by in silico analysis. In the present paper, the genealogic transmission of those polymorphic coding and noncoding variants of BRCA genes in family's members has been investigated. Thirty families, enrolled within the Genetic Counselling Program of our Institute, with probands and at least one-first degree relative (n = 67 family members) available, have been studied for both BRCA1 and BRCA2 pathological mutation and polymorphic variants' transmission. Ten and 6 probands carried Mendelian transmitted mutations in BRCA1 and BRCA2, respectively. Polymorphic coding and noncoding variants were transmitted in each family's relatives with a frequency ranging from 42 to 100%, with similar rate for each SNP in mutated and nonmutated families with the only exception of BRCA1 K1183R significantly more frequent in mutated families (P = 0.004); conversely, this SNP and BRCA2 N372H, were more frequently present in breast cancer relatives belonging to families in which pathological BRCA mutations were not present. Furthermore, specific haplotypes were transmitted in all relatives as BRCA1 871Leu-1038Gly, present in both BRCA mutated and nonmutated families, while BRCA2 289His-991Asp-IVS14+53 C>T present only in BRCAX families suggesting the harmful role of these SNPs. In conclusion, analysis of SNPs maps and modality of their transmission could identify further susceptibility markers and provide a basis for a better DNA-based cancer classification.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - Feb 2011



  • BRCA1
  • BRCA2
  • Breast cancer risk
  • Familiarity
  • Polymorphism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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