Clinical Cancer Genetics Flashcards
Inherited cancer susceptibility
Where does the mutations that cause cancer occur? (2)
- Constitutional (germline) -> heriditary, informs future cancer risk, informs treatment decisions, provides info for other family members -> Inherited cancer
- Somatic mutations (certain tissues) -> Acquired, informs treatment decisions + provides reassurance -> sporadic cancer
State the common genetic susceptabilities to cancer with their proportion?
- Sporadic (65%): Mostly due to DNA repair defects
- Familial cancer (25%): Multiple low risk cancer genes which accumulate to have high risk for cancer
- High risk cancer (10%): A single gene that greatly increases your risk of getting cancer
Describe what is multifactorial/polygenic familial risk
- Increased proportion of familial cancers than high risk cancer predisposition genes -> Risk conferred through multiple lower risk genetic factors +/- environmental factors
Are there any tests for multifactorial/polygenic familial risk?
- No current testing available
- Family history as a proxy of risk + increased screening is available for some cancer types in at risk individuals (e.g. breast, colorectal)
Describe the risk between cancer predisposition genes + polygenic risk?
CPG greatly increases risk of PR
Why identify patients with increased genetic predisposition to cancer?
- Informs medical management + surgical options
- Provides reasons why cancer developed
- Future cancer risk
- Identify potential relatives for screening
How can we identify patients with increased genetic predisposition to cancer?
- Genes in which germline mutations confer highly or moderately causing increased risks of cancer are called cancer predisposition genes
- Family history, pathology of cancer (genes), tumour testing + syndromic features, polygenic risk score
What is a polygenic risk score?
Genetic testing of multiple low risk factors
- Indicate increase genetic susceptibility to cancer
Explain how the polygenic cancer test is worked out
Undertaken by looking for cancer associated
SNPs via GWAS
How does tumour testing occur?
- Large cancer gene panel sequencing of their tumour
- If disease causing change found in cancer predisposition gene
- Possible might also be in germline
- Offer a blood test to check
Describe multifactorial/polygenic risk assessment?
- Larger proportion of familial cancers than high risk cancer predisposition genes (CPGs)
- No routine genetic testing
- Multiple lower risk genetic factors
- Family history as a proxy of risk
- Screening, Prevention and Early Detection (SPED) e.g. - Mammograms - Colonoscopies - Chemoprevention
When should you test for high risk CPG?
Likelihood of finding a pathogenic variant > 10% - via gene test
Why has genetic testing transitioned to whole-genome sequencing?
- An increase In mutation detection
- Understanding of mutagenesis
- Understanding of phenotypic spectrum/cancer risk if outside ‘typical syndrome’
State the outcomes of diagnostic genetic testing with management?
- No disease causing variant identified - M = family history + personal diagnosis
- Variant of uncertain significance identified -> Analyse variant, Manage on basis of personal and family history + more information to classify variant
- Disease causing (pathogenic) variant identified -> Manage as per gene specific protocol, offer cascade screening to relatives + SPED
Describe SPED methods if clinically actionable pathogenic variant is identified in CPG?
Screening - Non-invasive OR invasive imaging
- Often more frequent + younger age
- Allows for Chemoprevention + Risk reducing surgeries
