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

hyperplastic, neoplastic, inflammatory, hamartomatous, Lipomas,
etc

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

+ disorganisation of architecture

Villous:
MUCINOUS cells with nuclear enlargement, elongation, multi-layering and loss of polarity.

Exophytic, frond-like extensions

Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia

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

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
Key in mismatch repair genes

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 - left side cancer

Unexplained iron deficiency anaemia - right side cancer

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

Perineural 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

Question 25

What is the function of the colon?

Answer 25

Extraction of water from faeces
(electrolyte balance)

Faecal reservoir (evolutionary advantage)

Bacterial digestion for vitamins
(e.g. B and K)

Question 26

Why eating food cooked at high temperatures lead to colon cancer?

Answer 26

HCAs (Heterocyclic Amines) are activated to PhIP which undergoes further reactions to become mutagenic.

Question 27

What are some anti cancer food elements?

Answer 27

Vitamin C - ROS scavenger

Vitamin E - ROS scavenger

Isothiocyanates (cruciferous veg)

Polyphenols (green tea, fruit juice)

Question 28

How do polyphenols have their effect?

Answer 28

Activate MAPK -> Regulates phase 2 detoxifying enzymes to reduce DNA oxidation

Question 29

What’s the distribution of colon cancer cell grading?

Answer 29

~10% well differentiated

~ 70% moderately differentiated

~ 20% poorly differentiated

Question 30

What qualifies someone as high risk for a colon cancer screen?

Answer 30

Previous adenoma

1st Degree relative affected by colorectal cancer before the age of 45

2 affected first degree relatives

evidence of dominant familial cancer trait including colorectal, uterine, and other cancers

UC and Crohn’s disease

Hereditable cancer families (include other sites)