Pathophysiology, Epidemiology, Causes of Cancer

Question 1

What are the 6 hallmarks of cancer?

Answer 1

1. Sustaining proliferative signalling
2. Evading growth suppressors
3. Activating invasion and metastasis
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Resisting cell death

Question 2

Explain the hallmark: Evading growth suppressors

Answer 2

evasion of ‘contact inhibition’ and tumour suppressor protein pRb can be dysfunctional

Question 3

Explain the hallmark: Sustain proliferative signalling

Answer 3

ability to synthesise their own growth signals and reduce dependence on stimulation from normal tissue micro environment –> autocrine stimulation (positive feedback signalling loop)

Question 4

Explain the hallmark: Activating invasion and metastasis

Answer 4

ability to remodel basement membrane and disrupt endothelial cell-to-cell contact and epithelial-mesenchymal transition (loss of adherens junctions, expression of matrix-degrading enzymes, increased motility and heightened resistance to apoptosis)

Question 5

Explain the hallmark: Enabling replicative immortality

Answer 5

limitless replication potential. Deactivation of pRb and p53. Production of telomerase (maintains telomere length)

Question 6

Explain the hallmark: Inducing angiogenesis

Answer 6

growth of new blood vessels from existing vasculature via secretion of VEGF-A. Creates regions of hypoxia.

Question 7

Explain the hallmark: Resisting cell death

Answer 7

loss of p53 tumour suppressor function and upregulation of pro-survival factors + downregulation of pro-apoptotic factors

Question 8

Summarise the multi-step nature of cancer development (5)

Answer 8

1. Initiation - exposure to carcinogens, accumulation of mutations in the cell
2. Promotion - number of factors (microenvironment), allows cell to evade tumour suppression
3. Transformation - cell growth not inhibited by close-contact by surrounding cells and not needing to be anchored
4. Progression - increased tumour growth and invasion + angiogenesis
5. Metastasis - spread

Question 9

What are the risk factors for cancer? (8 listed)

Answer 9

1. Tobacco (carcinogen)
2. Diet (lack of fibre, processed/red meats, salt, saturated fats)
3. Obesity (increased oestrogen with reduced sex hormone binding globulin, increased insulin, increased oesophageal reflux, increased gallstone production)
4. Alcohol (aldehyde production, increased sex hormone levels, folate + Vit B deficiency)
5. Viruses (Hep B + C, HIV, HPV)
6. Environmental (sunlight, asbestos, redon)
7. Inactivity (Reduced oestrogen and insulin)
8. Family history (BRCA1/BRCA2, HNPCC)

Question 10

What are the three main checkpoints within the cell cycle?

Answer 10

1. G1/S checkpoint - monitors for insufficient cell growth and nutrient requirements
2. G2/M checkpoint - monitors for DNA damage and can prevent mitosis
3. M-phase checkpoint - monitors the chromosome alignment on mitotic spindle

G0 - cells exit and are in rest phase (do not replicate)

Question 11

Types of malignant cancer: Carcinoma (6 types)

Answer 11

85% of cancers

Epithelial tumour cells that begin in tissue that lines the inner or outer surfaces of the body.

1. Squamous cell carcinoma (flat-surface)
2. Adenocarcinoma (glandular cells)
3. Transitional carcinoma (cells that stretch)
4. Basal cell carcinoma (Cells at bottom of epidermis)
5. Ductal carcinoma in situ (early stage)
6. Invasive ductal carcinoma (beyond primary epithelial layer)

Question 12

Types of malignant cancer: Sarcoma

Answer 12

Mesenchymal tissue –> connective or other non-epithelial tissue

Question 13

Types of malignant cancer: Leukaemia

Answer 13

Haematopoietic tissue (bone marrow)
1. Acute
2. Chronic

Lymphoid or Myeloid

Question 14

Types of malignant cancer: Lymphoma

Answer 14

Haematopoietic tissue that develops from lymphocytes (lymphatic system)
1. Hodgkin’s
2. Non-Hodgkin’s - 90%

Question 15

Types of mutations in the DNA sequence (2 main)

Answer 15

1. Point mutation
   - Silent
   - Missense
   - Nonsense
2. Frameshift mutation
   - Addition of nucleotide(s)
   - Deletion of nucloetide(s)

Question 16

Types of mutations: chromosomal (5)

Answer 16

1. Duplication
2. Deletion
3. Insertion
4. Inversion
5. Translocation

Question 17

What are oncogenes?

Answer 17

Genes that promote cancer and can lead to the abnormal stimulation of the cell cycle.

Question 18

How do oncogenes occur? (3 ways)

Answer 18

1. Amplification of a chromosomal region containing proto-oncogenes
2. Translocation of DNA within the genome
3. Point mutations in the proto-oncogenes which alter protein function, or mutations to gene control elements, leading to an increase in gene expression

Question 19

What is the role of tumour-suppressor genes?

Answer 19

Help prevent uncontrolled cell growth by repairing damaged DNA, controlling cell adhesion, and inhibiting the cell cycle or cell-signalling pathway

Question 20

How do you approach cancer patient care (9 steps)

Answer 20

1. Diagnosis
2. Define extent of disease (staging/grading)
3. Define treatment intent
4. Manage complications of disease and treatment
5. Understand the biological behaviour of cancer within an individual patient
6. Recognise the limitations of treatment
7. Provide innovative/experimental treatment when possible
8. Look after cancer survivors
9. Provide palliative care

Question 21

What are the screening methods for the following cancers:

1. Cervical
2. Breast
3. Prostate
4. Bowel

Answer 21

1. Pap smear
2. Mammogram
3. Serum prostate-specific antigen
4. Faecal occult blood testing