L24: Clinical Cancer Genetics

Question 1

What are the two types of cancer mutations?

Answer 1

→constitutional germline

→somatic

Question 2

Compare germline mutations and somatic mutations

Answer 2

→germline and somatic inform inform treatment decision
→germline and somatic inform family members

→Germline informs future cancer risk

Question 3

What is family history used for in clinical cancer?

Answer 3

→as a proxy of risk

Question 4

Describe polygenic familial risk

Answer 4

→Risk conferred through multiple lower risk genetic factors +/- environmental factors

→No current testing available

→No single high risk gene identified

Question 5

What distribution does polygenic disease follow?

Answer 5

→normal distribution

Question 6

On a normal distribution graph, where is familial risk associated with?

Answer 6

→shifted to right hand side

Question 7

Why identify patients with increased genetic predisposition to cancer?

Answer 7

→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

Question 8

How can we identify patients with increased genetic predisposition to cancer?

Answer 8

→Family history
→Tumour testing
→Syndromic features eg features in tumour
→Pathology of cancer

Question 9

When are breast cancers most common?

Answer 9

→post menopausal

Question 10

What are polygenic risk scores?

Answer 10

→Genetic testing of multiple low risk factors

→indicate increased genetic susceptibility to cancer

Question 11

How are polygenic risk scores calculated?

Answer 11

→cancer associated SNPs found from Genome Wide Association Studies

Question 12

What are two common syndromic features of cancer?

Answer 12

→Mucocutaneous pigmentation

→Trichilemmoma- Causden syndrop

Question 13

What is the stratified prevention strategy?

Answer 13

→categorisation of the population into multiple groups with different interventions applied in the different groups

Question 14

What are CPGs?

Answer 14

→cancer predisposition genes

Question 15

What is involved in Screening, Prevention and Early Detection (SPED)?

Answer 15

→Mammograms
→Colonoscopies
→Chemoprevention

Question 16

What drug reduced bowel cancer risk?

Answer 16

→bowel

Question 17

What is the genotype of colon polyps?

Answer 17

→MUTYH gene

→recessive

Question 18

What are the four stages of genetic testing in cancer?

Answer 18

→Single gene
→NGS panel
→WES
→WGS

Question 19

What are the outcomes of diagnostic genetic testing?

Answer 19

→No disease causing variant identified

→Variant of uncertain significance identified

→Disease causing (pathogenic) variant identified

Question 20

What are the three types of Screening, Prevention and Early Detection (SPED)?

Answer 20

→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

Question 21

Which people have predictive testing?

Answer 21

→WELL person to predict future risk

Question 22

What happens if pathogenic variant is not present in a well person after predictive testing?

Answer 22

→manage as population risk

Question 23

What happens if pathogenic variant is present in a well person after predictive testing?

Answer 23

→manage as per gene specific protocol

Question 24

What are the most frequent monogenic causes of hereditary breast cancers?

Answer 24

→BRCA1 and BRCA2 genes

Question 25

What is BRCA1 involved in?

Answer 25

→DNA repair (homologous recombination repair)

→regulation of transcription

Question 26

Which groups of people are BRCA 1 common in?

Answer 26

→Polish, Ashkenazi Jewish

Question 27

What is recommended for male BRCA2 carriers?

Answer 27

→recommended to have annual PSA test

Question 28

What is one cause of Lynch syndrome?

Answer 28

→Mismatch repair

→MLH1, MSH2, MSH6 and PMS2

Question 29

How are carriers for Lynch syndrome managed?

Answer 29

→Screening
→Risk-reducing surgery
→Chemoprevention- Low dose aspirin
→Research
→Cancer management
→Family matters

Question 30

How is Lynch syndrome tested for?

Answer 30

→Loss of protein expression via IHC in tumour sample