Introduction to Cancer and Clinical Genetics

Question 1

List the commonest cancers

Answer 1

Prostate, Breast, Lung, Colorectal, Cervix, Bladder, Endometrial

Question 2

What are driver mutations?

Answer 2

allow cancer to grow & spread e.g. tumor suppressor gene, RAAS

Question 3

What are passenger mutations?

Answer 3

randomly spaced throughout the genome with no benefit to the cell as a result of rapid cell div & high mutation state

Question 4

What are kataegis?

Answer 4

Higher levels of mutations through specific locations of the genome

Question 5

What 3 factors does a cancer cell typically have?

Answer 5

• Have a mutation inactivating the TP53 gene
• A gain-of-function / activating mutation in a RAS or MYC proto-oncogene
• Activates Telomerase

Question 6

What is TP53?

Answer 6

It’s a Tumour Suppressor Gene (TSG) that encodes a protein called p53
Over half of human cancers have a TP53 mutation

Question 7

What is p53?

Answer 7

operates within the nucleus to:
• Activate DNA repair processes
• Arrest cell division if there is DNA damage
• Initiate apoptosis in severe DNA damage
• Control cell senescence

Question 8

What are proto-oncogenes?

Answer 8

• control cell proliferation signals

Question 9

What are oncogenes?

Answer 9

• mutated proto-oncogenes that are stuck in ‘on-mode’

- The cell can then divide without normal growth factor stimulation

Question 10

What are telomeres?

Answer 10

Structures at the end of our chromosomes that provide a protective cap
– ends get shorter as cell div so help prevent cell going through too many div processes
• They consist of a repetitive sequence of 6 nucleotides – TTAGGG
• With each cell division the number of times this sequence is repeated is reduced.

Question 11

What happens if telomeres are absent?

Answer 11

the chromosomes are prone to structural rearrangements, ultimately leading to senescence or apoptosis

Question 12

What happens to cancer cells telomere expression?

Answer 12

Cancer cells over-express Telomerase, which extends the telomeres
• Cellular immortality…

Question 13

What happens if TP53 mutation occurs from conception?

Answer 13

–> Li-Fraumeni Syndrome

Question 14

Which drug has halved the number of Lynch syndrome cases?

Answer 14

600mg aspirin

Question 15

How do anti-platelet drugs affect tumor cells?

Answer 15

Anti-platelet activity improves immune response to tumour cells
Platelets can stick to cancer cells but block immune system from then accessing tumor cells
Inducing apoptosis of tumour cells due to anti-inflammatory effects

Question 16

What is the benefit of salicylic acid?

Answer 16

• Metabolite of aspirin
• Acts in plants as a signalling hormone
• Mediates a broad spectrum systemic immune response

Question 17

List the symptoms of cancer

Answer 17

• Non-specific:
• Lethargy, tiredness, malaise, decreased exercise tolerance, unexplained weight loss
• Specific:
• Bleeding – PR, PV, haemoptysis, haematuria
• A lump
• Pain (often dull, longstanding)
• Persistent cough
• Dysphagia
• A change (bowel habit, micturition…)

Question 18

List the signs of cancer

Answer 18

• Non-specific:
• Cachexia, anaemia, tachycardia, tachypnoea, palpable metastases
• Specific
• Lump, skin tethering, nipple retraction (breast)
• Effusion, consolidation (lung)

Question 19

List the trajectory of a cancer pt

Answer 19

Diagnosis  
• History  
• Examination  
• Imaging  
• Biopsy  
• Staging  
• [Tumour genetics/genomics] – genetic testing of tumor • [Liquid biopsy – cell free circulating tumour DNA] – from blood sample, more accurate rep of diff types of DNA from tumor

Question 20

Describe cancer staging

Answer 20

• TNM system
• Tumour – 0, 1, 2, 3, 4
• Nodes – 0, 1 [regional node(s) only], 2, 3 [distant nodes] • Metastases – 0, 1

Question 21

What are the benefits of surgery as a cancer treatment

Answer 21

• Gives greatest chance of cure
• Stage 1 cancers and pre-invasive tumours often treated with surgery alone
Majority of solid tumour patients will have surgery as part of their management

Question 22

List Notable Surgical Advances

Answer 22

• Organ preservation surgery – preserve organ + just remove tumor
• Minimally invasive surgery i.e. keyhole
• Robot-assisted surgery – fine movements, tight spaces
• Intra-operative radiotherapy
• Curative intent metastasis surgery

Question 23

List the different aspects of Palliation

Answer 23

• Tumour reduction – surgery, chemotherapy, radiotherapy, targeted therapies
• Symptom management
• Holistic care
• Managing other health problems
• Rationalising medication
• Respecting wishes
• Spiritual care
• Family care

Question 24

What are the aims of screening?

Answer 24

• Requires evidence of improved outcome
• Different methods and efficacy for each cancer type
• Aim to detect pre-cancerous lesions

Question 25

Which aspects are important to consider for screening?

Answer 25

• Sensitivity and Specificity • Cost • Compliance/uptake • Natural history of tumour progression • Stage shift/mortality data Cervical and breast cancers have pre-cancerous stage which can turn into cancer