COLORECTAL CANCER Flashcards
Whats the incidence of colorectal cancer?
Common
13% of all cancer cases and 10% of cancer deaths in the UK
4th most common cancer
Second most common cause of cancer death
95% of pt are aged over 50 at time of diagnosis
Equally common in men and women
Incidence increasing due to ageing population but mortality is decreasing
What is the adenoma-carcinoma sequence?
Most colorectal cancers develop via a progression of normal mucosa to colonic adenoma (‘polyps’) to invasive adenocarcinoma
Adenomas may be present for >10 years before becoming malignant and 10% of adenomas progress to adenocarcinoma
Hyperproliferation of mucosa -> APC gene mutation -> early adenoma -> K-RAS mutation -> intermediate adenoma -> DCC mutation -> late adenoma -> p53 mutation -> adenocarcinoma
What genetic mutations are associated with colorectal cancer?
Adenomatous polyposis coli (APC) - note: more than half colon cancer show allelic loss of this gene
MSH-2, MSH6, MLH1, PMS2 (DNA mismatch repair genes) - HNPCC/lynch syndrome
Activation of the K-ras oncogene
Delection of DCC tumour suppressor gene
Deletion of P53 tumour suppressor gene
MYH - MYH-associated polyposis
Is colorectal cancer inherited?
Only 5% of cases are truly inherited
The vast majority occur spontaneously
What are adenomas?
a benign, dysplastic tumour of columnar cells or glandular tissue.
What are the hereditary syndromes that increase the risk of colorectal cancer?
Hereditary non polyposis colorectal cancer (lynch syndrome)
Familial adenomatous polyposis
MYH-associated polyposis
Serrated polyposis syndrome
Peutz-jeghers syndrome
Juvenile polyposis syndrome
What is HNPCC? What proportion of cases of colorectal cancer is it responsible for?
Autosomal dominant condition where there are mutations to DNA mismatch repair genes (usually MSH2 60% of cases or MLH1 in 30% of cases) 0 cases microsatellite instability
It increases the incidence of many malignancies (stomach, small intestine, bladder, skin, brain, hepatobilliary system, endometrial and ovarian cancer). Lifetime risk of colorectal cancer in mutation carriers is 70-80%
3%
What is FAP? What proportion will develop colorectal cancer?
an autosomal dominant condition arising from germiline mutations of The (APC) gene - a tumour suppressor gene.
Penetrance is virtually 100%
Accounts for <1% of all colorectal cancers
characterized by the presence of hundreds to thousands of colorectal and duodenal adenomas, some of which undergo malignant change.
90% will develop CRC before the age of 45 if not treated.
What screening is done for FAP?
Annual colonoscopies from age 12-14
Prophylactic surgical resection can be offered if anything is found
What is Gardner’s syndrome?
A form of FAP
It can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
What is MYH-associated polyposis?
An autosomal recessive condition characterised by colorectal adenomas and cancers caused by a mutation to MYH (MUT Y homologue) gene.
MUTYH is a base excision repair gene and failure of its normal action increases the risk of colorectal cancer.
What are serrated polyps?
a heterogeneous group of colorectal lesions that includes the benign hyperplastic polyps, and the pre-malignant sessile serrated adenoma and traditional serrated adenoma. They are characterized by the saw-tooth appearance of the crypt epithelium.
Supposedly BRAF gene mutations and gene promoter hypermethylation
What is peutz-jeghers syndrome? Whats the risk of colorectal cancer?
An autosomal dominant condition characterised by hamartomatous polyps in the gastrointestinal tract, pigmented mucocutaneous lesions and an increased risk of gastrointestinal and extragastrointestinal malignancies.
The polyps, which are hamartomas, can occur anywhere in the gastrointestinal tract but are most frequent in the small bowel.
There is an estimated 40% lifetime risk of colorectal cancer.
What is juvenile polyposis syndrome?
Autosomal dominant condition with incomplete penetrant
It is characterised by hamartomatous polyps throughout the GI tract but mainly found in the colon. It causes an increased risk of CRC and gastric cancer.
Occurs mainly in children and teenagers
Characterised by >3-5 juvenile colonic polyps, juvenile polyps throughout the GIT or any number of polyps with a family history
Polyps are a cause of bleeding and intussesception in the first decade of life
Whats the onset of cancer in lynch syndrome?
40-50 or younger (earlier than in sporadic cases!)
Whats the mean age of adenoma development in FAP? Whats the average age at which colorectal cancer develops?
16 years
39 years
How should FAP be managed?
Affected individuals should be offered a prophylactic colectomy
What is attenuated FAP?
A type of FAP which presents slater in life at about 44 years and has fewer polyps (<100) which tend to occur on the right side of the colon
What proportion of colorectal cancers originate from serrated polyps?
30%
What are the risk factors of colorectal cancer?
FHx of colorectal cancer/polyps - most common risk factor
Longstanding/chronic IBD
PMHx of colorectal cancer/polyps
Genetic syndrome e.g. FAP or lynch syndrome
Obesity
Red and processed meat
Eating too little fibre
Alcohol and smoking
Increasing age
Medical conditions - gallstones, diabetes, acromegaly
Radiation exposure
H.pylori infections
What are the protective factors for colorectal cancer?
Regular physical exercise
Dietary fibre
Non-starchy vegetables
Pulses
High calcium intake
Garlic
What proportion of cases of colorectal cancer have a positive family history?
10-20%
What are the most common sites for colorectal cancer to develop?
Rectum 40%
Sigmoid colon 30%
Caecum 15%
Transverse colon 10%
Descending colon 5%
(2/3rds occur distal to splenic flexure)
What proportion of colorectal cancers have metastatic spread at diagnosis?
25%