molecular basis of colon cancer

Question 1

what is Familial adenomatous polyposis

Answer 1

autosomal dominant genetic disease

causes 100s or thousands of polyps developing from adolescence

also lesions in the retina
low mutation rate
high cancer risk

Question 2

what is herediatary nonpolyposis colon cancer aka lynch syndrome

Answer 2

autosomal dominant
high risk of colon tumours 
linked to other tumours 
low numbers of polyps 
different genes are involved from DNA mismatch repair pathway 
high mutation rate
high cancer risk -80%

Question 3

what percentage of colorectal cancer patients have a family history

Answer 3

25%

Question 4

what is penetrance

Answer 4

how likely a person with the mutation is to get the cancer

Question 5

what is the gene defect in FAP

Answer 5

adenomatous polyposis coli tumour suppressor gene
chromosome 5
mostly nonsense or frameshift mutations

Question 6

how can you test for gene defects

Answer 6

direct sequencing or protein truncation test

Question 7

what is the 2 hit hypothesis

Answer 7

APC is a tumour suppressor gene

both copies of the gene must be damaged in order for cancer to develop

Question 8

how does APC function

Answer 8

binds to beta catenin and microtubules

stabilises the chromosomes during cell division

Question 9

what is beta catenin

Answer 9

binds to transcription factors
beta catenin stimulates cell division
also stabilises cells by tightly associating them with their adjacent cells
too much beta catenin is associated with colon cancer
regulated by APC protein
binds to T cell factor which promotes cell division
WnT pathway leading to proliferation of Gut stem cells

Question 10

what other problems might APC cause

Answer 10

•Gardner Syndrome
•Rare
•Variant of FAP
•Masses of benign tumours
•Jaw cysts
•Sebaceous cysts
•Osteomata
•pigmented lesions of
the retina (CHRPE)
chromosome instability

Question 11

who is screened for fecal occult blood

Answer 11

over 50s every 2 years

Question 12

what type of diet can reduce colon cancer risk

Answer 12

high fibre
low meat
high fish

Question 13

what other factors increase your colon cancer risk

Answer 13

obesity

alcohol

Question 14

how can cancer risk be reduced with aspirin

Answer 14

decreases prostaglandin which stimulates proliferation and angiogenesis
inhibits apoptosis

Question 15

what is the most common mutation in hereditary non polyposis

Answer 15

MLH1

microsatellite instability

Question 16

compare and contrast FAP and HNPCC

Answer 16

both have high cancer risk
fap- large number of polyps but low mutation rate
HNPCC- low number of polyps but high mutation rate

fap risk - 100%, HPNCC- 80%
age of onset is approx 40

biannual colonoscopy

Question 17

what constitutes a high to moderate risk of colon cancer

Answer 17

• people with three or more affected
relatives in a first degree kinship with each
other (none less than 50 years old)
• two affected relatives less than 60 years
old in a first degree kinship with each
other, or two affected relatives with a
mean age less than 60 years old in a first
degree kinship

Question 18

when is cetuximab used

Answer 18

wildtype Kras

Question 19

what is the increased risk of colon cancer if overweight or obese

Answer 19

overweight - 25%

obese 50%

Question 20

which NSAID may reduce risk

Answer 20

aspirin - inhibits cox 2