Colorectal Cancer

Question 1

What are the predominant risk factors for CRC?

Answer 1

aging
personal hx ofr CRC or adenomas
high fat and charred meat diet
inflammatory bowel disease
FHx of CRC
hereditary cancer syndromes

Question 2

General population risk of CRC:

Answer 2

6%

Question 3

What’s your risk for CRC if you have a personal hx?

Answer 3

15-20%

Question 4

CRC risk if you have inflammatory bowel disease?

Answer 4

15-40%

Question 5

CRC risk if you have a HNPCC (Lynch) mutation?

Answer 5

60-80%

Question 6

CRC risk if you have FAP?

Answer 6

> 95% (due to sheer number of polyps)

Question 7

What’s your risk if no FHX of CRC?

Answer 7

2%

Question 8

CRC risk with one 1st degree relative?

Answer 8

6%

Question 9

CRC risk with one 1st and one 2nd degree relative w CRC?

Answer 9

8%

Question 10

CRC risk if you have. a1st degree relative dx <45y?

Answer 10

10%

Question 11

CRC risk if you have 2 1st degree w/ CRC?

Answer 11

17%

Question 12

What % of CRC is sporadci?

Answer 12

65-85%

Question 13

What % of CRC is familial?

Answer 13

10-30%

Question 14

What % of CRC is caused by Lynch syndrome? What types of genes are these?

Answer 14

2-3%, MMR

Question 15

what % of CRC is caused by FAP?

Answer 15

1%

Question 16

At what stage do polyps become malginant?

Answer 16

once they become adenocarcinomas

Question 17

What stages are before adenocarcinoma in the carcinogenesis of CRC?

Answer 17

hyperproliferation
small polyp
large polyp
severe dysplasia

Question 18

What’s the most common type of polyp? malignant?

Answer 18

hyperplastic, rarely

Question 19

What types of polyps have low malignant potential?

Answer 19

imflammatory and hamartomatous

Question 20

What types of polyps are hamartomatous?

Answer 20

juvenile and Peutz-Jeghers

Question 21

What types o polyps are usually the most malignant?

Answer 21

adenomatous

Question 22

What gene is associated with FAP?

Answer 22

APC

Question 23

What’s the penetrance of APC mutation for polyps and cancer w/o management?

Answer 23

roughly 100

Question 24

What other cancers are ppl with FAP at risk for?

Answer 24

upper GI
desmoid
osteoma
thryoid
brain
hepatoblastoma (ped liver)

Question 25

What else can be present with FAP?

Answer 25

CHRPE

Question 26

What areas, after colon, most commonly develop cancer in FAP?

Answer 26

small intestine and upper GI

Question 27

What's different about aFAP and FAP?

Answer 27

aFAP: - more moderate phenotype - later onset (CRC age 50y) - not associated with chrpe - UGI lesions

Question 28

How is FAP inherited? What % of mutations are de novo?

Answer 28

AD 25%

Question 29

How do you surveil aFAP? FAP?

Answer 29

``` full colonoscopy (later teens) colonoscopy or sigmoidoscopy (age 10-15) ```

Question 30

What are the characteristics of MUTYH-associated polyposis?

Answer 30

15

Question 31

How is MUTYH-associated polyposis inherited?

Answer 31

AR 30% have identifiable mutations

Question 32

What are some other polyposis syndromes?

Answer 32

Hereditary mixed poylposis syndrome Sessile serrated poylposis Oligodontia-CRC syndrome

Question 33

What 4 MMR genes are associated with Lynch syndrome? What other gene is involved?

Answer 33

MLH1, MSH2, PMS2, MSH6, EPCAM

Question 34

Around what age does somenoe with Lynch syndrome get diagnosed with CRC?

Answer 34

45y

Question 35

Mutations in MLH1 and MSH2 may also result in cancers of the:

Answer 35

endometrium and ovaries

Question 36

What % of people with Lynch syndrome present with synchronous CRC? Metachronous?

Answer 36

20% syn 40% met. within 10 yrs

Question 37

The Amsterdam criteria is also known as the:

Answer 37

3-2-1 rule

Question 38

Describe the 3-2-1 rule.

Answer 38

- 3 or more relatives with HNPCC associated cancer - At least two successive generations affected - one or more cancer by the age of 50

Question 39

What two things are reported on tumor studies?

Answer 39

MSI and IHC

Question 40

What type of MSI is more prevalent in Lynch syndrome?

Answer 40

high

Question 41

If MLH1 and PSM2 are both absent from tumor then it is most likely a germline mutation in:

Answer 41

MLH1

Question 42

If MSH2 and MSH6 are both absent from tumor then it is most likely a germline mutation in:

Answer 42

MSH2 or EPCAM

Question 43

If MSH6 is absent from tumor then it is most likely a germline mutation in:

Answer 43

MSH6

Question 44

If PMS2 is absent from tumor then it is most likely a germline mutation in:

Answer 44

PMS2

Question 45

Roughly 90% of Lynch families have mutations in:

Answer 45

MLH1 or MSH2

Question 46

What types of testing is done for GI cancers?

Answer 46

mostly cover Polyposis and Lynch, TP53 included fro Li-Fraumeni