General considerations

Oxford American handbook of oncology. Second Edition. Oxford University Press (2015)

Genetic mutations that predispose to cancer are best considered as syndromes increasing the risk of cancer in many different organs, rather than just one organ. Although many syndromes have associated lists of criteria meant to guide referral for genetic evaluation, attention to a number of basic features can help in identifying appropriate patients:

  • Cancer in two or more close relatives on the same side of the family
  • Early age of onset (below 40 for most syndromes)
  • Multiple primary tumors
  • Bilateral disease in paired organs
  • Multiple rare cancers in one family
  • For most syndromes, evidence of autosomal dominant transmission

Patients and families demonstrating these characteristics are reasonable candidates for referral to a genetics specialist or genetic counselor.

Critical in this process is collecting a reasonably detailed family history, including the following:

  • A t least three generations of family history information
  • Some estimate of total number of individuals in each generation to determine how many potential at-risk members are present in the family
  • Information on ethnic ancestry, because some populations have a higher prevalence of well defined “founder” mutations

Important elements of counseling for genetic testing are as follows:

  • Determine whether testing is available for suspected syndrome
  • Implications for screening and management with a positive or negative test
  • Risk of passing mutation to children and risk to other family members, including siblings
  • Assessment of psychological stress and family dynamics
  • Discussion of discrimination considerations (health and life insurance, employment), although these concerns have not been strongly evident in clinical practice
  • Discussion of testing accuracy: sensitivity, specificity, and possibility of genetic variation of unknown significance

Several useful models are available for evaluating family cancer histories.

  • For example, the BRCAPR O model is a validated model using Baysian analysis of family histories to give pretest probabilities for carrying a BRCA1/2 mutation.
  • This model is part of the CAGene software, available free with registration at:
  • This software package will also give estimates for carrying genes causing other cancer syndromes.

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