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Cancer genetics

  • Several germline mutations have been shown to increase cancer risk
  • More than 50 genetic abnormalities have been identified
  • Most are inherited in autosomal dominant fashion
  • Cancer genetics are important as:
    • Genes involved are important in normal growth and development
    • Improve our knowledge of cancer biology
    • Allow identification of high-risk patients who will benefit from preventative therapies
  • Most genetic abnormalities involve tumour suppressor genes
  • Code for proteins that are important in normal growth and development
  • Hereditary cancer syndromes result from germline mutation in one copy of the suppressor gene
  • Somatic mutation in the second copy of the gene results in the development of cancer

 Breast cancer genetics

  • 12% women will develop breast cancer in their life-time
  • 5% breast and ovarian cancers due to germ-line mutation

BRCA1 and BRCA2 genes

  • BRCA1 and BRCA2 are tumour suppressor genes
  • Commonest abnormality is in BRCA1 gene found on long arm of chromosome 17
  • Mutation seen in 50% of families with 4 or more affected members < 60 years
  • More than 100 BRCA mutations described
  • Highest carrier rate is in Ashkenazi Jews
  • If a patient is BRCA1 positive she has:
    • 50% risk of developing breast cancer by 50 years
    • 85% risk of developing breast cancer by 70 years
    • 70% risk of developing contralateral breast cancer
    • 50% life time risk of developing ovarian cancer


  • How should BRCA1 and BRCA2 positive patients be managed ?
  • Possible options include:
    • Intensive screening with annual mammography from an early age
    • Chemoprophylaxis with tamoxifen
    • Prophylactic mastectomy
  • Reduces but does not completely abolish risk of breast cancer
  • Risk of ipsilateral and contralateral recurrence is higher in BRCA1 and BRCA2 carriers


Emery J,  Lucassen A,  Murphy M.  Common hereditary cancers and implications for primary care.  Lancet 2001;  358:  56-63.

Haffty B G,  Harrold E,  Khan A J et al.  Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 2002;  359:  1471-1477.

Taylor M R G.  Genetic testing for inherited breast and ovarian cancer syndromes:  important concepts for the primary care physician.  Postgrad Med J 2001;  77:  11-15.


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