Skip to main content


Log in

Mutations and polymorphic BRCA variants transmission in breast cancer familial members

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.


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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others


  1. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517

    Article  CAS  PubMed  Google Scholar 

  2. Sehl ME, Langer LR, Papp JC, Kwan L, Seldon JL, Arellano G, Reiss J, Reed EF, Dandekar S, Korin Y et al (2009) Associations between single nucleotide polymorphisms in double-stranded DNA repair pathway genes and familial breast cancer. Clin Cancer Res 15:2192–2203

    Article  CAS  PubMed  Google Scholar 

  3. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC et al (2008) The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 98:1457–1466

    Article  CAS  PubMed  Google Scholar 

  4. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093

    Article  CAS  PubMed  Google Scholar 

  5. Imyanitov EN (2009) Gene polymorphisms, apoptotic capacity and cancer risk. Hum Genet 125:239–246

    Article  PubMed  Google Scholar 

  6. Freedman ML, Penney KL, Stram DO, Riley S, McKean-Cowdin R, Le Marchand L, Altshuler D, Haiman CA (2005) A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk. Cancer Res 65:7516–7522

    Article  CAS  PubMed  Google Scholar 

  7. Hughes DJ (2008) Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Fam Cancer 7:233–244

    Article  CAS  PubMed  Google Scholar 

  8. Tommasi S, Pilato B, Pinto R, Monaco A, Bruno M, Campana M, Digennaro M, Schittulli F, Lacalamita R, Paradiso A (2008) Molecular and in silico analysis of BRCA1 and BRCA2 variants. Mutat Res 644:64–70

    CAS  PubMed  Google Scholar 

  9. Tommasi S, Crapolicchio A, Lacalamita R, Bruno M, Monaco A, Petroni S, Schittulli F, Longo S, Digennaro M, Calistri D et al (2005) BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from Apulia, Italy. Mutat Res 578:395–405

    CAS  PubMed  Google Scholar 

  10. Berry DA, Iversen ES Jr, Gudbjartsson DF, Hiller EH, Garber JE, Peshkin BN, Lerman C, Watson P, Lynch HT, Hilsenbeck SG et al (2002) BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol 20:2701–2712

    Article  CAS  PubMed  Google Scholar 

  11. Dunning AM, Chiano M, Smith NR, Dearden J, Gore M, Oakes S, Wilson C, Stratton M, Peto J, Easton D et al (1997) Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum Mol Genet 6:285–289

    Article  CAS  PubMed  Google Scholar 

  12. Olden K (2007) Commentary: from phenotype, to genotype, to gene-environment interaction and risk for complex diseases. Int J Epidemiol 36:18–20

    Article  PubMed  Google Scholar 

  13. Lange EM, Sun J, Lange LA, Zheng SL, Duggan D, Carpten JD, Gronberg H, Isaacs WB, Xu J, Chang BL (2008) Family-based samples can play an important role in genetic association studies. Cancer Epidemiol Biomarkers Prev 17:2208–2214

    Article  PubMed  Google Scholar 

Download references


Partially supported by Regione Puglia (DIEF 2007).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Stefania Tommasi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pilato, B., Martinucci, M., Danza, K. et al. Mutations and polymorphic BRCA variants transmission in breast cancer familial members. Breast Cancer Res Treat 125, 651–657 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: