Colorectal Cancer Flashcards
What are the predominant risk factors for CRC?
aging personal hx ofr CRC or adenomas high fat and charred meat diet inflammatory bowel disease FHx of CRC hereditary cancer syndromes
General population risk of CRC:
6%
What’s your risk for CRC if you have a personal hx?
15-20%
CRC risk if you have inflammatory bowel disease?
15-40%
CRC risk if you have a HNPCC (Lynch) mutation?
60-80%
CRC risk if you have FAP?
> 95% (due to sheer number of polyps)
What’s your risk if no FHX of CRC?
2%
CRC risk with one 1st degree relative?
6%
CRC risk with one 1st and one 2nd degree relative w CRC?
8%
CRC risk if you have. a1st degree relative dx <45y?
10%
CRC risk if you have 2 1st degree w/ CRC?
17%
What % of CRC is sporadci?
65-85%
What % of CRC is familial?
10-30%
What % of CRC is caused by Lynch syndrome? What types of genes are these?
2-3%, MMR
what % of CRC is caused by FAP?
1%
At what stage do polyps become malginant?
once they become adenocarcinomas
What stages are before adenocarcinoma in the carcinogenesis of CRC?
hyperproliferation
small polyp
large polyp
severe dysplasia
What’s the most common type of polyp? malignant?
hyperplastic, rarely
What types of polyps have low malignant potential?
imflammatory and hamartomatous
What types of polyps are hamartomatous?
juvenile and Peutz-Jeghers
What types o polyps are usually the most malignant?
adenomatous
What gene is associated with FAP?
APC
What’s the penetrance of APC mutation for polyps and cancer w/o management?
roughly 100
What other cancers are ppl with FAP at risk for?
upper GI desmoid osteoma thryoid brain hepatoblastoma (ped liver)
What else can be present with FAP?
CHRPE
What areas, after colon, most commonly develop cancer in FAP?
small intestine and upper GI
What’s different about aFAP and FAP?
aFAP:
- more moderate phenotype
- later onset (CRC age 50y)
- not associated with chrpe
- UGI lesions
How is FAP inherited? What % of mutations are de novo?
AD
25%
How do you surveil aFAP? FAP?
full colonoscopy (later teens) colonoscopy or sigmoidoscopy (age 10-15)
What are the characteristics of MUTYH-associated polyposis?
15
How is MUTYH-associated polyposis inherited?
AR
30% have identifiable mutations
What are some other polyposis syndromes?
Hereditary mixed poylposis syndrome
Sessile serrated poylposis
Oligodontia-CRC syndrome
What 4 MMR genes are associated with Lynch syndrome? What other gene is involved?
MLH1, MSH2, PMS2, MSH6, EPCAM
Around what age does somenoe with Lynch syndrome get diagnosed with CRC?
45y
Mutations in MLH1 and MSH2 may also result in cancers of the:
endometrium and ovaries
What % of people with Lynch syndrome present with synchronous CRC? Metachronous?
20% syn
40% met. within 10 yrs
The Amsterdam criteria is also known as the:
3-2-1 rule
Describe the 3-2-1 rule.
- 3 or more relatives with HNPCC associated cancer
- At least two successive generations affected
- one or more cancer by the age of 50
What two things are reported on tumor studies?
MSI and IHC
What type of MSI is more prevalent in Lynch syndrome?
high
If MLH1 and PSM2 are both absent from tumor then it is most likely a germline mutation in:
MLH1
If MSH2 and MSH6 are both absent from tumor then it is most likely a germline mutation in:
MSH2 or EPCAM
If MSH6 is absent from tumor then it is most likely a germline mutation in:
MSH6
If PMS2 is absent from tumor then it is most likely a germline mutation in:
PMS2
Roughly 90% of Lynch families have mutations in:
MLH1 or MSH2
What types of testing is done for GI cancers?
mostly cover Polyposis and Lynch, TP53 included fro Li-Fraumeni
