Inherited cancer genetics

Question 1

What are the 2 types of Mutation?

What is Multifactorial/Polygenic Familial Risk?

How do you identify patients with a higher genetic predisposition to cancer?

Answer 1

• 1. Germline - Hereditary, Informs future cancer risk and treatment decisions, Provides information for other family members
     
     2. Somatic - Acquired, Informs treatment decisions, Provides reassurance for family and future children
• • No single high-risk gene identified
  • Risk conferred through multiple lower-risk genetic and environmental factors
• • Family history - Cancer type, Age of onset, Multiple similar cases
  • Syndromic features
  • Tumour testing
  • Pathology of cancer - Cancer type and the gene affected

Question 2

Outcomes of diagnostic genetic testing:
What do you do when no pathogenic variant is identified?

What do you do when a variant of uncertain significance is identified?

What do you do when a Pathogenic variant is identified?

Answer 2

• Manage on basis of family history and personal diagnosis
• • Analyse variants
  • Try to get information to help classify a variant
  • Manage on basis of personal and family history
• • Manage as per gene-specific protocol
  • Can offer cascade screening to relatives

Question 3

Examples:
How do you manage a patient with Hereditary Breast and Ovarian cancer?

How do you manage a patient with Lynch Syndrome?

Answer 3

• • Screening
  • Risk-reducing surgery
  • Chemoprevention
• • Screening - Colorectal, Gastric, Symptom awareness
  • Risk-reducing surgery - Hysterectomy +/- removal of both ovaries (BSO)
  • Chemoprevention - Low dose aspirin
  • Cancer management