Cancer as a Disease – Colorectal Cancer

Question 1

What type of carcinoma are most colon cancers?

Answer 1

Adenocarcinoma

Question 2

What is the rate of turnover of cells in the colon?

Answer 2

2-5 million cells per minute

- high proliferation rate social ells are vulnerable to mutation

Question 3

What is a polyp?

Answer 3

Any projection from a mucosal surface into a hollow viscus

Question 4

What is an adenoma?

Answer 4

Benign neoplasm of the mucosal epithelial cells

Question 5

What are the different types of colonic polyp?

Answer 5

Metaplastic/hyperplastic 
Adenoma
Juvenile
Lipomas
Peutz jeghers

Question 6

State some characteristics of hyperplastic polyps.

Answer 6

These are VERY COMMON
90% of all colonic polyps
They have NO malignant potential
15% have K-ras mutations

Question 7

What are the different types of colonic adenoma?

Answer 7

Tubular
Tubulovillous
Villous
NOTE: the more villous it is the worse it is

Question 8

What are the different shapes of colonic adenomas?

Answer 8

Pedunculated – on a stalk- looks like a tree

Sessile – flat and raised looks like a hedge

Question 9

What is the difference between tubular and villous adenomas?

Answer 9

Tubular– COLUMNAR cells with nuclear enlargement, elongation, multi-layering and loss of polarity + increased proliferative activity + reduced differentiation

Villous– MUCINOUS cells with nuclear enlargement, elongation, multi-layering and loss of polarity. May be exophytic.

Question 10

What is the most famous condition that causes an increased number of colonic polyps?

Answer 10

Familial Adenomatous Polyposis

Question 11

What gene mutation is FAP caused by?

Answer 11

5q21

Question 12

What are the two genetic pathways in colorectal cancer?

Answer 12

1. Adenoma-carcinoma sequence = presence of adenomas will increase the risk of colorectal cancer
2. Microsatellite instability

Question 13

What are microsatellites?

Answer 13

Repeat sequences of DNA that are prone to misalignment

Some microsatellites are found in coding sequences of genes which inhibit growth or are involved in apoptosis

Question 14

State two genetic diseases that predispose to colorectal cancer.

Answer 14

1. Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
2. HNPCC – microsatellite instability (affects mismatch repair genes)

Question 15

State some dietary factors that can increase the risk of colorectal cancer.

Answer 15

High fat
Low fibre
High red meat
Refined carbohydrates

Question 16

State two dietary deficiencies that can increase the risk ofcolorectal cancer.

Answer 16

1. Folates– important for nucleotide synthesis and DNA methylation
2. MTHFR (Methylenetetrahydrofolate reductase) – deficiency leads to disruption of DNA synthesis and DNA instability (this leads to mutation). It also causes decreased methionine synthesis leading to genomic hypomethylation and focal hypermethylation – this can have gene activating and silencing effects

Question 17

What is the clinical presentation of colorectal cancer?

Answer 17

1. Change in bowel habit
2. PR bleeding
3. Unexplained iron deficiency anaemia

Question 18

Describe the distribution of colorectal cancer.

Answer 18

RECTOSIGMOID –55%
Caecum/Ascending –22%
Transverse –11%
Descending –6%

Question 19

Describe the Dukes classification of colorectal cancers.

Answer 19

Dukes A

• Growth is limited to the wall (muscularis propria)
• Nodes negative

Dukes B

• Growth beyond the muscularis propria
• Nodes negative

Dukes C1

• Nodes positive
• Apical nodes negative

Dukes C2
- Apical nodes positive

Question 20

State some clinical features that affect the prognosis of colorectal cancer.

Answer 20

1. Bowel obstruction (diminished prognosis)
2. Age < 30 (diminished prognosis)
3. Distant metastases (diminished prognosis)

Question 21

State some pathological features that affect the prognosis of colorectal cancer.

Answer 21

1. Depth of bowel wall penetration
2. Number of regional lymph nodes involved
3. Venous invasion
4. Lymphatic invasion

Question 22

What are the criteria for a screening programme?

Answer 22

Condition should be important with respect to the seriousness and/or frequency
The natural history of the disease must be known in order to: Identify where screening can take place
To enable the effects of any intervention to be assessed

Question 23

What are the characteristics of a screening test?

Answer 23

Simple and acceptable to the patient
Sensitive and selective
Cost effective
Screening population should have equal access to the screening procedure

Question 24

What does the NHS colorectal cancer screening look for?

Answer 24

Faecal occult blood (FOB)
If positive and 55-60 years = sigmoidoscopy
If positive and over 60-75 years = full colonoscopy

Question 25

Of cancers how common is colorectal cancer?

Answer 25

4th common cancer worldwide

2nd cause of death in cancers after lung cancer

Question 26

What does a mutation in APC cause?

Answer 26

cell proliferation

prevents cell loss

Question 27

What % of adults have adenomas at 50? What % of these becomes cancers if left?

Answer 27

25%

then 5% become cancer if left

Question 28

What foods can have anti-carcinogenic elements?

Answer 28

1. Vitamin C and E- ROS (reactive oxygen species) scavengers
2. Isothiocyanates- cruciferous vegetables-auliflower, cabbage, garden cress, bok choy, broccoli, Brussels sprouts and similar green leaf vegetables.
3. Polyphenols- green tea and fruit juice
   - can activate MAPK pathways regulating phase 2 metabolism to detoxify enzymes

Question 29

What is the function of the colon?

Answer 29

Extraction of water from faeces
Faecal reservoir
Bacterial digestion for vitamin. production