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4 clinical genetics (w/out IEM) > intro to clinical cancer genetics > Flashcards

intro to clinical cancer genetics Flashcards

1
Q

What can we do to reduce cancer risk in people at increased genetic risk?

A

Screening
Prevention
Early Detection

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2
Q

SNP - what is it and what does it increase the risk of?

A

single. nucleotide polymorphism, change from 1 base to another

SNP’s increase the risk of cancer

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3
Q

2 DNA strands - what are they and how are they read?

A

anti-parallel
One strand ‘read’ 5’ to 3’
Other strand read 3’ to 5’

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4
Q

Genetic variation may…

A

influence our chance of developing disease

Inherited cancer risk

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5
Q

external factors that can affect DNA?

A

smoking
exposure to UV
drugs

these cause a permanent change to the DNA - mutation

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6
Q

2/3 of cancers are “sporadic” - what does this mean?

A

acquired (somatic) mutations within a cell in cancer genes, driving the cell to become cancerous

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
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7
Q

what is meant by inherited cancer risk?

A

genetic changes we are born with which increase the risk of developing cancer

  1. High risk changes - cancer predisposition genes
  2. Moderate risk changes
  3. Low risk changes
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8
Q

which genes are rare?

A

High risk cancer predisposition genes

  • if you have one, you have a high chance of developing cancer in your lifetime (9 out of 10 chance)
  • rare variants, large effect
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9
Q

which genes are more common?

A

Low risk genetic changes

  • -common variants in the population, increases your cancer risk by a very small amount
  • having multiple of these lower risk variants means you are more likely to develop cancer than the avg person in the population
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10
Q

Clustering of the same types of cancer indicates what?

A

a multifactorial risk

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11
Q

role of Genome Wide Association Studies

(GWAS) and Polygenic Risk Scores?

A

looking at cases and controls, seeing single base substitutions that are more common in cases than controls

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12
Q

Inherited cancer risk can be split into what?

A

having high risk genes (10%) and familial cancer (25%)

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13
Q

give examples of High risk cancer predisposition genes?

A 
Breast cancer			5-10%	BRCA
Ovarian 				10%		BRCA
Colon 				5-10%	Lynch
Melanoma			10%		CDKN2A
Medullary thyroid		25%		RET
Retinoblastoma		40%		RB1
Prostate				5-10%	BRCA2
Pancreatic			10%		BRCA2

% shows how how likely it is that the cancer was caused by a high risk gene

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14
Q

Working out someone’s genetic risk for cancer

A

3 generational family history assessment, looking for:

  • a young age of onset
  • multiple cancer diagnoses of same type in closely related individuals
  • multiple cancer diagnoses of cancer related to specific CPG in closely related individuals
  • consider ethnic origin

also consider the types of cancer in detail to see if they increase the chance of a high risk cancer predisposition gene (CPG)

Look for any rare syndromic features which could indicate a high risk cancer predisposition gene

Use the National Genomic Test Directory Eligibility Criteria to decide if genetic testing is indicated

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15
Q

Tumour testing may identify?

A

genetic changes which could indicate inherited risk – need to check with a blood test

e.g.
Immunohistochemistry of mismatch repair genes in Lynch Syndrome
BRCA gene sequencing in ovarian cancer

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16
Q

Decisions to make on assessment

A

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?

17
Q

Management of inherited cancer risk

A
  1. Offer screening, prevention and early detection advice (SPED)

Assess the family history and give a risk percentage - anything over a 30% lifetime risk of getting cancer is deemed high risk

people will get screening regularly or annually etc. depending on whether they are green or yellow group

  1. Chemoprevention
    - taking medication to reduce breast cancer risk (eg. tamoxifen, Selective estrogen reuptake moderator – SERM - side effects – hot flushes, sexual dysfunction)
    - colorectal cancer: aspirin
  2. High risk CPGs : Genetic testing considerations
    - in terms on the individual, look at their risks of other cancers
    - sharing info to relatives
    - family planning options
18
Q

Diagnostic versus predictive testing

A

Diagnostic testing
To confirm whether a CPG has caused the cancer

Predictive testing
To identify if an unaffected person carries a CPG

19
Q

Outcomes of testing

A
  1. No genetic variant identified
    - Reassuring for patient
    - referral for screening
    - management of family history
  2. Disease causing variant in CPG identified
    - Screening and management tailored to specific CPG
    - Should be reviewed by NHS clinical genetics service
  3. 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, but they need to understand how common genetic variation is and that most VUS are benign
20
Q

Sporadic cancer vs cancer due to CPG

A

Hereditary cancers

  • 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

  • No increased risk of other cancers
  • Usually small increased risk to relatives
  • No genetic testing indicated
  • Normal clinical management for affected individuals
21
Q

Germline vs somatic mutations

A

germline

  • present in egg or sperm
  • can be inherited -cause cancer family syndrome
  • all cells affected in offspring

Somatic

  • acquired
  • occurs in nongermline tissues
  • cannot be inherited

4 clinical genetics (w/out IEM) (4 decks)

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