Colon cancer Flashcards
what organs are part of the gut?
- oesophagus
- gallbladder
- liver
- stomach
- pancreas
- duodenum (first part of small intestine)
- small intestine
- colon (large intestine)
- rectum
what are the unique features of colorectal cancer?
- 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)
what is the APC involved in , in the gut?
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
what is another type of colon cancer?
Hereditary Non-Polyposis Colon Cancer
- involves changes in mismatch repair genes
what is the incidence of colon cancer?
- 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
where do most bowel cancers develop?
in the lower descending colon, sigmoid colon or rectum
colon cancer risk factors
- age
- obesity
- high alcohol intake
- smoking
- diet
- genetics
- inflammation
how does diet increase risk
- red meat
- processed meat
how does genetics increase risk
- 5% due to inherited predispositions
- 1% familial adenomatous polyposis
- hereditary non-polyposis (lynch syndrome) early onset
how does inflammation increase risk
- crohn’s disease and ulcerative colitis predisposition
- anti inflammatories (aspirin) protect
symptoms of bowel cancer?
- abdominal pain
- weight loss
- anaemia
- diarrhoea
- bloated feeling
- nausea
- constipation
- blood in stool
- mucus
- altered bowel habit
how is colon cancer diagnosed?
- 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
treatment of colon cancer
- 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
what chemotherapy is used?
- 5FU and oxaloplatin
- Irinotecan + 5FU + Folinic acid
- avastin
what is the difference between a colonoscopy and sigmoidoscopy?
- colonoscopy examines the entire length of the colon
- sigmoidoscopy examines only the lower 1/3
what is the barium enema?
- valuable diagnostic tool
- helps detect abnormalities in the large intestine (colon)
screening: blood in the stool test
- being offered on NHS
- anyone over 70 yrs can request a screening kit
- NHS will process the test
- appointment if needed
disadvantages of screening blood in the stool test
- 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
what is stage one of colon cancer?
confined to inner mucosal lining; 10% patients
survival; 80%
what is stage two of colon cancer?
grown into muscle wall ; 35%
survival; 60-70%
what is stage three colon cancer?
spread to at least one lymph node; 25%
survival; 30-60%
what is stage four colon cancer?
spread to remote organs; 30%
survival; 15%
what does Wnt do?
binds to Frizzled and allows cells to proliferate by allowing activation of b-catenin
what happens to b-catenin in wild type villi?
no Wnt-receptor binding; b-catenin is off therefore, cell cycle arrested; b-catenin destroyed by proteosome
what to b-catenin in APC+ villi?
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
where does b-catenin activity happen?
where the villi is connected to the intestinal lumen
what is a ‘vogelgram’?
concept that depicts how cancer is caused by sequential mutations of specific oncogenes and TSGs
- deals only with somatic mutations
what is the pathway of colon cancer?
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
changes that cause CRC
- lost APC function (80% of sporadic CRC)
- gain-of-function of b-catenin by mutation
what are the effects of APC truncation?
- 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
