Colorectal Cancer Flashcards
Sporadic CRC
There is no family history of CRC or other predisposing condition. Sporadic CRC accounts for about 70% of all CRCs. It is most common over the age of 50 and the risk of developing sporadic CRC increases with age.
Familial CRC
About 25% of new CRC cases are familial in nature. Affected patients have a family history of CRC, but the pattern is not consistent with one of the inherited syndromes described (eg. Father diagnosed with CRC at 75 years; maternal aunt diagnosed with CRC at 68 years).
Individuals from these families are at increased risk of developing CRC, although the risk is not as high as with the inherited syndromes.
Inherited CRC syndrome
Less than 10% of new CRC cases are due to inherited or germline cause. Inherited CRCs are broken down according to whether or not multiple colonic polyps preceed a cancer diagnosis.
Polyposis syndromes, include but are not limited to familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). Inherited syndromes without an obvious polyposis phenotype are referred to as nonpolyposis CRC, the most common of which is Lynch syndrome.
Synchronous cancers
Two or more primary carcinomas can coexist at the time of diagnosis
Metachronous cancers
Cancers that develop in succession over time
Polyposis
Phenotype having hundreds or even thousands of polyps, most often seen in hereditary conditions such as familial adenomatous polyposis (FAP); individuals with dozens of polyps are often referred to as having attenuated polyposis
Non-polyposis
A phenotype having few to no polyps preceeding a colon cancer diagnosis, often seen in hereditary conditions such as Lynch syndrome
Adenoma-to-carcinoma sequence
The sequence of events by which an adenomatous polyp becomes increasingly dysplastic and gain invasive potential.
Typically takes about 10 years in sporadic CRCs, but is accelerated in inherited CRC syndromes.
Major mechanisms that drive CRC
- Chromosomal instability pathway (CIN)
- Defective DNA mismatch repair (MMR)
- CpG island methylation pathway (CIMP)
ATC progression
Microsatellites
Regions of repetitive nucleotide sequences, where DNA mismatch is likely to occur.
CpG Island Methylation Pathway of CRC development
This pathway to CRC formation initially relies on mutations in the BRAF oncogene followed by CpG island methylation of an MMR gene or TSG.
If MSH/MLH genes are silenced by aberrant methylation, this may lead to microsatellite instability.
Shapes of polyp
Lynch Syndrome
- Autosomal dominant
- Mutation in mismatch repair pathway gene
- MLH1, MSH2, MSH6, and PMS2
- Nonpolyposis CRC syndrome, also w/ endometrial and ovarian cancer
- 20-80% risk of developing during lifetime, average onset ~45 y.o.
- LoH of the affected gene leads to aberrant DNA damage and cancer development
Lynch syndrome risk factors that indicate performing a diagnostic test
Familial Adenomatous Polyposis
- Autosomal dominant, however, 1/3 cases are de novo
- Caused by LoF in the APC TSG
- LoH leads to cancer development
- Present w/ polyposis phenotype
- Lifetime risk of CRC is 100% in absence of colectomy
- Other cancers in syndrome are duodenal, thyroid, and CNS
- Extra teeth or osteomas are also common in these individuals
Risk stratification in CRC
The American Cancer Society recommends beginning colonoscopys creening for all average-risk patients at age __.
The American Cancer Society recommends beginning colonoscopys creening for all average-risk patients at age 45.
Stool-based CRC screening
- Based on the detection of exfoliated colonocytes and blood from colorectal adenomas and cancers.
- Patients with positive tests require additional evaluation with colonoscopy and in patients with negative results screening must continue to be performed frequently in order to be effective
- Up to 40% of patients do not adhere to the schedule of annual testing over a period of several years, and nearly one third of those with stool tests that are positive for occult blood do not undergo follow-up evaluation.
Fecal IHC test
- Detects human globin in stool
- FIT is more specific for lower gastrointestinal bleeding as globin from an upper gastrointestinal bleeding source is digested in transit.
- FIT screening is more expensive as compared with gFOBT but unlike gFOBT, FIT screening is performed on a single stool sample, and is overall a more effetive screening test for CRC than gFOBT.
Fecal DNA test
- Testing for mutations/oncogenes from cells shed off in the stool
- Cologuard is a multi-target stool DNA test (MT-sDNA)
- Process of MT-sDNA testing requires the contents of an entire bowel movement
- May also detect malignancy in upper GI tract
Extent of sigmoidoscopy vs colonoscopy
Colonoscopy has the benefit of being both a ___ and ___ test.
Colonoscopy has the benefit of being both a diagnostic and therapeutic test.
Complications during colonoscopy
- Those due to sedation (hypoxia, aspiration, cardiac arrhythmia)
- Those due to bowel preparations (electrolytes and fluid shifts, abdominal discomfort, nausea, vomiting)
- Risk of bleeding (especially on polyp removal)
- Risk of perforation
- Exogenous infection due to contaminated colonoscopy equipment
