Bowel cancer - Pathology and the screening process Flashcards

1
Q

Where does bowel cancer have a high incidence?

A

High incidence in western world; low incidence in Asia and Central Africa

Bowel cancer affects men and women equally

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2
Q

Risk factors for bowel cancer

A
  • Migration from a low risk population to a high risk population
  • Foods rich in red meat and fat increase risk of bowel cancer
  • Longstanding ulcerative colitis
  • Crohn’s disease - to a lesser extent than UC
  • Presence of adenoma in the large bowel
  • Previous history of bowel cancer surgery
  • Family history of bowel cancer
  • Old age
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3
Q

What factors reduce the risk of bowel cancer?

A

Physical activity and low BMI are associated with low risk of cancer

Foods rich in veg, fruit and fibre

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4
Q

How do foods rich in veg, fruit and fibre reduce the risk of bowel cancer?

A

Increase in faecal bulk and reduces transit time

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5
Q

How does high fibre diet reduce bowel cancer?

A
  • Increases formation of short chain fatty acids which promote healthy gut microbes which induce differentiation, arrest growth of cells and cause apoptosis
  • By increasing stool bulk, thereby reducing stool transit time –> potential carcinogens in the stool have a shorter contact with the bowel mucosa
  • By reducing secondary bile acid formation which are potentially carcinogenic
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6
Q

What is a polyp?

A

Polyp is a protrusion into a hollow viscus, can be benign adenoma or malignant

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7
Q

What is an adenoma?

A

Pre-cancerous lesions

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8
Q

What type of epithelium do adenomas consist of?

A

Dysplastic epithelium

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9
Q

What type of feature is low grade dysplasia?

A

Early precancerous feature

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10
Q

What type of feature is high grade dysplasia?

A

Advanced precancerous feature, high risk of invasion if not removed

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11
Q

What are pathological features of polyps?

A

Hyperplastic, tubular adenoma, villous adenoma, tubulovillous adenoma

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12
Q

What is hyerplasia in polyps?

A

More goblet cells than normal mucosa; has a lace-like pattern

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13
Q

What is familial adenomatus polyposis?

A
  • Hundreds to thousands of polyps in large bowel, 500-2500

- Minimum of 100 polyps required to make diagnosis of FAP

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14
Q

Why are the polyps called adenomas?

A

Polyps are dysplastic

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15
Q

Where does FAP increase the risk of cancer?

A

Duodenum

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16
Q

What is the defective gene in FAP?

A

Chr 5q21

17
Q

What is the defective gene in FAP also called?

A

Adenomatous polyposis coli (APC)

18
Q

What is the first hit in FAP?

A

Patients acquire the first abnormal gene in utero as germ cell mutation

19
Q

What is the second hit in FAP?

A

To develop polyps they acquire the second genetic abnormality in the somatic cells

20
Q

What is the two hit hypothesis to develop FAP?

A

Patient is born with a single genetic abnormal(first hit) and acquires the second genetic abnormality(second hit) after birth

21
Q

What does the two hit hypothesis explain?

A

Explains hereditary retinoblastoma, cancer of the eye in children and is applicable to most cancers

22
Q

What is loss of heterozygosity?

A
  • With one copy of the abnormal gene, the cells are heterozygous
  • The loss of the second set of normal genetic material during the ‘second hit’ is termed loss of heterozygosity and cells will acquire two identical copies of abnormal genes
  • Cells acquire more genetic abnormalities to progress with adenoma-carcinoma sequence after the second hit
23
Q

Describe step 1 of the adenoma-carcinoma process

A

Normal mucosa - Inherited or acquired mutations(1st hit) loss of APC 5q21

24
Q

Describe step 2 of the adenoma-carcinoma process

A

Hyperproliferative epithelium - Methylation abnormalities(2nd hit) Loss of APC 5q21

25
Q

Describe step 3 of the adenoma-carcinoma process

A

Early adenoma - Mutation K-R AS gene 12p12

26
Q

Describe step 4 of the adenoma-carcinoma process

A

Intermediate adenoma - Loss of tumour suppressor gene SMAD2 and 4 18q21

27
Q

Describe step 5 of the adenoma-carcinoma process

A

Late adenoma - Loss of tumour suppressor gene p53 17p13

28
Q

Describe step 6 of the adenoma-carcinoma process

A

Invasive cancer - Telomerase activity to maintain immortality

29
Q

What is hereditary non-polyposis colorectal cancer/lynch syndrome?

A

Familial cancer affecting predominantly the caecum and right colon, before the age of 50

30
Q

What is lynch syndrome also associated with?

A

Endometrial, ovarian, small bowel and cancer of the urinary tract

31
Q

Genetics of HNPCC/lynch syndrome

A
  • Errors due to mismatch in the DNA causes expansion and contractions of these repeat nucleotides causing microsatellite instability
  • Defective copy of the mismatch repair gene in utero is inherited in first hit and acquire the second copy during life(second hit) and develop cancer
32
Q

What are four examples of mismatch genes involved in pathogenesis in HNPCC?

A
  • MSH2(2p16) and MLH1(3p21) - 30% of the HNPCC

- PMS1 and PMS2

33
Q

What is the amsterdam criteria for assessing for HNPCC?

A
  • Three or more relatives with HNPCC-associated cancer
  • One affected patient should be a first-degree relative of the other two
  • Two or more successive generations should be affected
  • Cancer in one or more affected relatives should be diagnosed before the age of 50 years
  • Familial adenomatous polyposis should be excluded in any cases of colorectal cancer
  • Tumours should be verified by pathological examination
34
Q

Symptoms of bowel cancer

A
  • Can be detected during screening
  • Change in bowel habit, constipation alternating with diarrhoea due to obstructive cancer
  • Bleeding from rectum
  • Anaemia especially with cancers of the caecum