L24: Clinical Cancer Genetics Flashcards
What are the two types of cancer mutations?
→constitutional germline
→somatic
Compare germline mutations and somatic mutations
→germline and somatic inform inform treatment decision
→germline and somatic inform family members
→Germline informs future cancer risk
What is family history used for in clinical cancer?
→as a proxy of risk
Describe polygenic familial risk
→Risk conferred through multiple lower risk genetic factors +/- environmental factors
→No current testing available
→No single high risk gene identified
What distribution does polygenic disease follow?
→normal distribution
On a normal distribution graph, where is familial risk associated with?
→shifted to right hand side
Why identify patients with increased genetic predisposition to cancer?
→Informs medical management and surgical options
→Informs relatives about cancer risk –access to screening / risk reducing surgery
→Provides reason for why developed cancer
→Informs patient about future cancer risk
How can we identify patients with increased genetic predisposition to cancer?
→Family history
→Tumour testing
→Syndromic features eg features in tumour
→Pathology of cancer
When are breast cancers most common?
→post menopausal
What are polygenic risk scores?
→Genetic testing of multiple low risk factors
→indicate increased genetic susceptibility to cancer
How are polygenic risk scores calculated?
→cancer associated SNPs found from Genome Wide Association Studies
What are two common syndromic features of cancer?
→Mucocutaneous pigmentation
→Trichilemmoma- Causden syndrop
What is the stratified prevention strategy?
→categorisation of the population into multiple groups with different interventions applied in the different groups
What are CPGs?
→cancer predisposition genes
What is involved in Screening, Prevention and Early Detection (SPED)?
→Mammograms
→Colonoscopies
→Chemoprevention
What drug reduced bowel cancer risk?
→bowel
What is the genotype of colon polyps?
→MUTYH gene
→recessive
What are the four stages of genetic testing in cancer?
→Single gene
→NGS panel
→WES
→WGS
What are the outcomes of diagnostic genetic testing?
→No disease causing variant identified
→Variant of uncertain significance identified
→Disease causing (pathogenic) variant identified
What are the three types of Screening, Prevention and Early Detection (SPED)?
→Non-invasive imaging –often more frequent and starting at younger age
→Invasive – often more frequent, starting at younger age
→Chemoprevention
→Risk reducing surgeries- removal of organs
Which people have predictive testing?
→WELL person to predict future risk
What happens if pathogenic variant is not present in a well person after predictive testing?
→manage as population risk
What happens if pathogenic variant is present in a well person after predictive testing?
→manage as per gene specific protocol
What are the most frequent monogenic causes of hereditary breast cancers?
→BRCA1 and BRCA2 genes
What is BRCA1 involved in?
→DNA repair (homologous recombination repair)
→regulation of transcription
Which groups of people are BRCA 1 common in?
→Polish, Ashkenazi Jewish
What is recommended for male BRCA2 carriers?
→recommended to have annual PSA test
What is one cause of Lynch syndrome?
→Mismatch repair
→MLH1, MSH2, MSH6 and PMS2
How are carriers for Lynch syndrome managed?
→Screening →Risk-reducing surgery →Chemoprevention- Low dose aspirin →Research →Cancer management →Family matters
How is Lynch syndrome tested for?
→Loss of protein expression via IHC in tumour sample
