Clinical Cancer Genetics Flashcards
Where do mutations occur?
germline or somatic
How is knowing germline mutations useful?
informs future cancer risk
Informs treatment decisions
provides info for other family members
Compare common to rare variants and the effects size
Most common variants have smallest effect size - implicated with common disease
rare variants cause mendelian disease
How many high risk predisposition are usually in familial risk?
Multifactorial/polygenic risk - no single high risk gene detected, usually multiple lower risk genetic factors and environmental factors
high risk cancer predisposition genes are rare
Which cancer types have some chance of high risk cancer predisposition genes (familial risk from single gene depending on cancer)?
Breast, colon, prostate, ovarian, melanoma
Why do we need to identify patients with increased genetic predisposition to cancer?
Informs medical management and surgical options
Provides reasons why cancer developed
Informs patient about future cancer risk
Informs relatives about cancer risk - access to screening , early detection and risk reducing surgery
How do we identify patients with increased genetic predisposition to cancer once they have developed the cancer?
Family history (multifactorial or polygenic risk)
Syndromic features (type of cancer)
Tumour testing
Pathology of cancer and molecular features
Cancer history
Personal history
Polygenic risk scores
What factors do we look for in a family history in pedigree chart showing those that have canceR?
Multiple cancers in same individual
Young age on onset
Multiple cancer diagnosis os same type in closely related individuals
Multiple cancer
What are polygenic risk scores?
Genetic testing of multiple low risk factors to indicate increased genetic susceptibility to cancer
How are polygenic risk scores found?
Look for cancer associated SNPs from GWAS (genome wide association studies)
test to see if cancer patients have more of a specific mutation compared to controls
What are constitutional mutations?
same thing as germline mutations - just another way to say it
What can inherited susceptibility to cancer be caused by?
Multifactorial/polygenic risk
HIgh risk cancer predisposition gene
How do you know if cause if multifactorial or high risk gene?
More people in family tree all closely linked have = high risk gene
Spread out and not many people = multifactorial
What is stratified prevention?
categorising everyone into risk groups, and those at higher risk are screened for often to prevent (e.g. mammogram for above 47 yrs old) or have intervention + family history taken
What is the guidlines for offering scrrening for cancer?
Identify people with high polygenic multifactorial risk and use family history
- can not due SNP testing, (GWAS only does that for research purposes)
Which type of inherited cancer is most common?
Familial cancer is higher than high risk cancer predisposition genes (CPGs)
Give examples of screening, prevention and early detection
Mammograms
Colonscopies
Chemoprevention
When is high risk CPG (high risk genes) tested for?
If likelihood of finding pathogenic variant is higher then 10%
Is recessive or dominant autosomal inheritance of high risk genes (CPGs) higher risk?
Autosomal dominant inheritance (50% chance of passing on). one gene enough for predisposition
When does autosomal recessive inheritance cause predisposition to cancer?
If healthy carriers passes on 2 pathogenic variants (one from each parent), child with both variants has the predisposition to certain cancers not the parents with one gene each
Give an example of a recessive high risk gene
MUTYH gene gives predisposition to colon polyps and cancer
Which autosomal dominant cancer predispositions are linked to autosomal recessive conditions?
BRCA2 in fanconi anaemia gene
ATM gene causing ataxia telangiectasia
What different diagnostic genetic testing can be done once cancer is discovered?
Single gene - test for known gene for specific cancer
NGS panel (more than 1 gene for specific cancer) - most common test
WES , WGS - too much infor
What happens in diagnostic genetic testing if no. disease causing variant is found as the cause of cancer
Manage based on family history and personal diagnosis
