Clinical Cancer Genetics Flashcards
What can we do to reduce cancer risk in people at increased genetic risk
Screening
Prevention
Early Detection
DNA - define
A molecule which contains the human genetic code
Genes - define
The instructions to tell the body how to grow, develop and function
Consist of sections of DNA which the cell translates into proteins
~ 20,000 genes in the human genome
2 copies of most genes – one on each chromosome
The human genome - define
The human genome
The entire length of DNA contained in human cells
3 billion bases
Explain importance of genetic variation
We have around 5 million different genetic changes compared to another unrelated person
Genetic variation makes us unique
Genetic variation may influence our chance of developing disease
Sporadic cancers - define
Most cancers are “sporadic” – due to acquired (somatic) mutations within a cell
giving it a growth advantage
Acquired mutations in cancer genes “drive” the cell to become cancerous
Not inherited changes
Explain risk of genetics in cancer - high/low
High risk cancer predisposition genes are rare
Low risk genetic changes increasing cancer risk are more common
Describe cancers occur due to inherited genetic changes
A smaller proportion of cancers occur due to inherited genetic changes
These can be multiple lower risk genetic variants – this is known as multifactorial or polygenic risk
Or a single high risk genetic variant in a cancer predisposition gene
Testing of the cancer - describe 2 parts
Pathology: certain pathological subtypes of cancers increase risk of high risk CPGs
Molecular testing: Tumour testing may identify genetic changes which could indicate inherited risk – need to check with a blood test
List 2 syndromic features - cancer
trichilemmoma
Mucocutaneous pigmentation
Decisions to make on assessment of cancer
Is there an increased inherited risk of cancer?
How high is the risk?
Does the patient need genetic testing to look for high risk cancer predisposition genes?
- Usually around a 1 in 10 chance of finding a mutation in a high risk cancer predisposition gene
Does the patient and/or their relatives need extra screening or other measures to reduce cancer risk?
How do we decide if genetic testing is indicated in cancer
Use the National Genomic Test Directory Eligibility Criteria to decide if genetic testing is indicated
Management of inherited cancer risk - method types
Offer screening, prevention and early detection advice (SPED)
Management of inherited cancer risk - Implications for individual
Recurrence risks
Risks of other cancers
Management of inherited cancer risk - Implications for relatives
How to share information
Concerns about children
Family planning options (e.g. prenatal, PGD)
Diagnostic versus predictive testing
`Diagnostic testing:
To confirm whether a CPG has caused the cancer
Predictive testing:
To identify if an unaffected person carries a CPG
Insurance implications
- Current moratorium for predictive testing
Outcomes of testing if no genetic variant identified
No genetic variant identified:
Screening and management on personal and family history
Referral for screening/further management only if indicated on above assessment
Reassuring for patient but reiterate participation in population screening programmes
Outcomes of testing if disease causing variant in CPG identified
Screening and management tailored to specific CPG
Should be reviewed by NHS clinical genetics service
Outcomes of testing if variant of uncertain significance (VUS) identified
Benign until proven guilty
Referral for screening/further management only if indicated on above assessment
May be anxiety provoking for patient. Need to understand how common genetic variation is and that most VUS are benign
Hereditary cancers - characteristics
High risks of recurrence/other associated cancers
High cancer risks in relatives
We can offer testing to at risk individuals
We can offer screening and preventative management to gene carriers
May alter treatment of affected individuals
Sporadic cancers - characteristics
No increased risk of other cancers
Usually small increased risk to relatives
No genetic testing indicated
Normal clinical management for affected individuals
Germline vs somatic mutation
G = entire OG carries mutation Present in sperm Can be inherited Cause cancer family syndrome Half of gametes carry mutation
S = patch of affected area
Occur in nongermline tissues
Cannot be inherited
S = non of gametes carry mutation
