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

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

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 – looks like a tree

Sessile – 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 increasednumber 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

Adenoma-carcinoma sequence = presence of adenomas will increase the risk of colorectal cancer
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

Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
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

Folates– important for nucleotide synthesis and DNA methylation
MTHFR– 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

Change in bowel habit
PR bleeding
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

Bowel obstruction (diminished prognosis) 
Age < 30 (diminished prognosis) 
Distant metastases (diminished prognosis)

Question 21

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

Answer 21

Depth of bowel wall penetration
Number of regional lymph nodes involved
Venous invasion
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 years = full colonoscopy