Clinical Cancer Genetics Flashcards
Where do cancerous mutations occur?
Constitutional/Germaline mutations
Somatic mutations - most common
Describe how constitutional/germaline mutations can cause cancer
- hereditary
- informs future risk of cancer
- informs treatment decisions
- provides information for other family members
Describe how somatic mutations can cause cancer
Acquired
Informs treatment decisions
Provides reassurance for family and future children
What is meant by multifactorial/polygenic familial cancer risk?
Makes up a large proportion of familial cancers
No single high risk gene has been identified
Risk conferred through multiple lower risk genetic factors and environmental factors
No current testing available
family history is used as a proxy of risk
What are the chances of finding high risk cancer predisposition genes?
Rare
Dependent on cancer type
Eg. Retinoblastoma 40%, breast cancer 5-10%
Why is it important to identify patients with increased genetic predisposition to cancer?
- informs medical management and surgical options
- informs relatives about cancer risk
- informs patient about future cancer risk
- provides reason for why developed cancer
How can we identify patients with increased genetic predisposition to cancer?
Family history
Syndromic features
Tumour
Pathology of cancer
What are polygenic risk scores?
Genetic testing of multiple low risk factors - by looking for cancer associated SNPs found from genome wide association studies.
It currently performed in NHS
Can indicate increased genetic susceptibility to cancer
What is meant by stratified prevention?
Risk assessment and assignment of interventions to several risk strata
Appropriate interventions for each striatum
How are people with high risk genes tested?
Family history
Syndromic features
Pathology of cancer
Tumour testing
Describe the process of genetic testing?
Way of testing genes varies based on tumour type
Single gene - more specific identification of cancer type
NGS panel
WES
WGS - very unsure of cancer
What are the 3 possible outcomes of a genetic test?
No disease causing variant identified (manage on basis of family history and personal diagnosis)
Variant of uncertain significance identified (analysis variant with scientists, try to get information to class variant if possible)
Disease causing variant identified (manage as gene specific protocol, can offer cascade screening to family)
What happens if a clinically actionable pathogenic variant is identified in CPG?
Manage according to gene specific protocol
Screening , prevention and early detection (SPED)
- non invasive imaging
- invasive
- chemo prevention
- risk reducing surgeries
When are predictive tests used?
A test in a well person to predict future risk
If pathogenic variant not present can manage as population risk usually
If pathogenic variant present, manage
What is hereditary breast and ovarian cancer syndrome?
BRCA1 and BRCA2 are the most frequent monogenic causes for hereditary breast cancers.
Account for 20% of familial breast cancer
Involved in DNA repair and regulation of transcription
Disease-causing variants result in an increased risk to develop certain cancers.
Founder mutations common in specific populations (eg. Polish and Jewish)
