Biology of colon cancer

Question 1

Describe colorectal cancer

Answer 1

• one of the most common causes of cancer
• unique features = mutations of single gene are present in most sporadic tumours and familial adenomatous polyposis, an inherited bowel cancer syndrome. Gene specifies the adenomatous polyposis coli protein (APC)
• multifunctional protein involved in many aspects of gut biology
• promote cell migration, regulate microtubule function in cell division and promote cell maturation through its regulation of beta-catenin
• another type of colon cancer = hereditary non-polyposis colon cancer = change in mismatch repair genes
• new screening strategies based on detection of mutant APC genes in stool (digital PCR) or in blood

Question 2

What is the incidence of colorectal cancer?

Answer 2

• 35,000 in UK
• 2/3 of cancers in colon
• 1/3 in rectum
• v few in small colon

Question 3

Where are colorectal cancers found?

Answer 3

• 15% transverse colon
• 5% descending
• 25% sigmoid
• 20% rectum
• 10% rectosigmoid
• 25% ascending/cecum

Question 4

What are the risk factors of colorectal cancer?

Answer 4

• age and obesity inc risk, exercise dec risk
• high alcohol intake, smoking
• diet - low fat high fibre beneficial red meat, processed meat = inc risk
• genetics - 5% due to inherited predispositions - familial adenomatous polyposis
• inflammation - crohns disease and ulcerative colitis predispose, anti-inflammatories to protect

Question 5

What are the symptoms of bowel cancer?

Answer 5

• abdominal pain
• weight loss
• anorexia
• diarrhoea
• nausea
• bloated feeling
• blood in stool
• mucus

Question 6

How is colorectal cancer diagnosed?

Answer 6

• physician examination of lower abdomen - palpable lump
• sigmoidoscopy/colonoscopy - to examine large intestine can also remove polyps
• barium enema = X ray bowel and its shape
• CT scan or US
• treatment = surgery/colonectomy
• effective is diagnoses early
• 90% alive at 5 years (localised)
• if advanced - spread to lymph nodes = only 50% alive at 5 years
• chemotherapy - advances disease (5FU and oxaloplatin)

Question 7

What is a colonoscopy/sigmoidoscopy?

Answer 7

• tube with camera - inserted into colon

- sigmoidoscopy examines only lower 1/3

Question 8

What is the barium enema?

Answer 8

• valuable diagnostic tool that helps detect abnormalities in the large intestine. The barium enema, along with colonoscopy remain standards in the diagnosis of colon cancer

Question 9

What are the screening methods - blood in stool

Answer 9

• bowel cancer screening offered on NHS
• anyone 70 years of age and over can request screening kit
• NHS will process test
• problems = false positives
• expect 2 of every 100 samples can be positive in the test - offer colonoscopy
• expect only 6 out of each 100 positives to have bowel cancer

Question 10

What are the stages of colorectal cancer?

Answer 10

I = confined to inner mucosal (10%)
II gown into muscle wall (35%)
III spread to at least one lymph node (25%)
IV spread to remote organ (30%)
five year survival stages I-IV (80%, 60-70%, 30-60% 15%)

Question 11

What is the vogelgram?

Answer 11

• model showing pathway to cancer
• normal epithelium (loss of APC) —> hyperplastic epithelium (DNA hypothmethylation) —>early intermediate and late adenomas (activation of K-ras, loss of 18q TSG) (loss of p53) —> carcinoma —> invasion and metastasis

Question 12

What are the effects of APC truncation?

Answer 12

• slower cell migration - greater exposure to carcinogens in lumen
• misregualtion of beta-catenin
• altered microtubule interactions causing = mis-segregation of chromosomes at cell-division
• the CIN (chromosome instability) phenotype, a common feature of colorectal cancer

Question 13

What are the new screening methodologies?

Answer 13

• cognizant of the genetic progression in bowl cancer

- digital PCR and BEAMing for mutant screening