Colon cancer

Question 1

what organs are part of the gut?

Answer 1

• oesophagus
• gallbladder
• liver
• stomach
• pancreas
• duodenum (first part of small intestine)
• small intestine
• colon (large intestine)
• rectum

Question 2

what are the unique features of colorectal cancer?

Answer 2

• mutations of a single gene are present in sporadic tumors AND cause familial adenomatous polyposis, an inherited bowel cancer symptom
• specific gene is the adenomatous polyposis Coli protein (APC)

Question 3

what is the APC involved in , in the gut?

Answer 3

APC is a multifunctional protein
- promotes cell migration
- regulate microtubule function in cell division
- promote cell maturation and differentiation through its regulation in b-catenin
- mutations in APC inhibit these processes

Question 4

what is another type of colon cancer?

Answer 4

Hereditary Non-Polyposis Colon Cancer
- involves changes in mismatch repair genes

Question 5

what is the incidence of colon cancer?

Answer 5

• 106,000 new cases per year in USA & 35,000 in UK
• 2/3 cancers in colon
• 1/3 in rectum
• very few in small colon

Question 6

where do most bowel cancers develop?

Answer 6

in the lower descending colon, sigmoid colon or rectum

Question 7

colon cancer risk factors

Answer 7

• age
• obesity
• high alcohol intake
• smoking
• diet
• genetics
• inflammation

Question 8

how does diet increase risk

Answer 8

• red meat
• processed meat

Question 9

how does genetics increase risk

Answer 9

• 5% due to inherited predispositions
• 1% familial adenomatous polyposis
• hereditary non-polyposis (lynch syndrome) early onset

Question 10

how does inflammation increase risk

Answer 10

• crohn’s disease and ulcerative colitis predisposition
• anti inflammatories (aspirin) protect

Question 11

symptoms of bowel cancer?

Answer 11

• abdominal pain
• weight loss
• anaemia
• diarrhoea
• bloated feeling
• nausea
• constipation
• blood in stool
• mucus
• altered bowel habit

Question 12

how is colon cancer diagnosed?

Answer 12

• physician examination of lower abdomen; palpable lump
• sigmoidoscopy/colonoscopy; to examin large instesinve, can also remove polyps
• barium enema; x-ray of bowel and its shape
• CT Scan or Ultrasound

Question 13

treatment of colon cancer

Answer 13

• surgery/colonectomy; effective is diagnosed early
• 90% alive at 5-years; localised cancer
• if advanced; spreads to lymph nodes, only 50% alive at 5 years
• chemotherapy if advanced disease

Question 14

what chemotherapy is used?

Answer 14

• 5FU and oxaloplatin
• Irinotecan + 5FU + Folinic acid
• avastin

Question 15

what is the difference between a colonoscopy and sigmoidoscopy?

Answer 15

• colonoscopy examines the entire length of the colon
• sigmoidoscopy examines only the lower 1/3

Question 16

what is the barium enema?

Answer 16

• valuable diagnostic tool
• helps detect abnormalities in the large intestine (colon)

Question 17

screening: blood in the stool test

Answer 17

• being offered on NHS
• anyone over 70 yrs can request a screening kit
• NHS will process the test
• appointment if needed

Question 18

disadvantages of screening blood in the stool test

Answer 18

• false positives
• 2/100 to be positive; ofer colonoscopy
• only 6/100 positives will have bowel cancer
• threfore over 90% of colonoscopies will be negative

Question 19

what is stage one of colon cancer?

Answer 19

confined to inner mucosal lining; 10% patients
survival; 80%

Question 20

what is stage two of colon cancer?

Answer 20

grown into muscle wall ; 35%
survival; 60-70%

Question 21

what is stage three colon cancer?

Answer 21

spread to at least one lymph node; 25%
survival; 30-60%

Question 22

what is stage four colon cancer?

Answer 22

spread to remote organs; 30%
survival; 15%

Question 23

what does Wnt do?

Answer 23

binds to Frizzled and allows cells to proliferate by allowing activation of b-catenin

Question 24

what happens to b-catenin in wild type villi?

Answer 24

no Wnt-receptor binding; b-catenin is off therefore, cell cycle arrested; b-catenin destroyed by proteosome

Question 25

what to b-catenin in APC+ villi?

Answer 25

Wnt binds/activates receptor; axin removed from b-catenin which binds to LEF TF , act in nucleus to activate gene expression and proliferations, site of future polyp formation

Question 26

where does b-catenin activity happen?

Answer 26

where the villi is connected to the intestinal lumen

Question 27

what is a ‘vogelgram’?

Answer 27

concept that depicts how cancer is caused by sequential mutations of specific oncogenes and TSGs
- deals only with somatic mutations

Question 28

what is the pathway of colon cancer?

Answer 28

normal epithelium; loss of APC; creates hyperplastic epithelium; DNA hypomethylation occurs; early adenoma; activaiton of KRAS; intermediate adenoma; loss of TSG; late adenoma; loss of p53; carcinoma; invasion and metastasis

Question 29

changes that cause CRC

Answer 29

• lost APC function (80% of sporadic CRC)
• gain-of-function of b-catenin by mutation

Question 30

what are the effects of APC truncation?

Answer 30

• slower cell migration; greater exposure to carcinogens in lum
• mis-regulation of b-catenin
• altered microtubule interactions = mis-segregation of chromosomes at cell division
• chromosome instability