Lec 30 Flashcards
What are 4 strong risk factors for colorectal cancer?
- age > 50
- country of birth
- hereditary syndrome
- longstanding IBD
What are 3 protective factors for colorectal cancer?
- physical activity
- aspirin/NSAIDs
- colonoscopy
How long does it generally take to go from polyp formation to cancer?
5-10 years
Is colorectal cancer more predominant in left vs right colon?
pretty even; maybe slightly more in left colon
Which type of adenomas are most likely to become cancerous?
- larger
- villous
- sessile
- more severe dysplasia
What type of plasia is an adenoma?
dysplasia
What characterizes colon dysplasia?
cytological abnormalities –> loss of goblet cells, increased nuclear: cytoplasm ratio
distorted crypt morphology
What fraction of adenomas progress to cancer?
5-10%
What are the 3 pathways of colon carcinogenesis?
- chromosomal instability
- microsatellite instability
- CpG island methylation
What is the chromosomal instability path of colon carcinogenesis?
normal mucosa –> loss of APC gene –> at risk –> K-ras mutation –> adenoma formation –> loss of tumor suppressor p53, DCC –> carcinoma
What is the microsatellite instability path of colon carcinogenesis?
have mutation/loss of DNA mismatch repair gene
increased mutations lead to cancer
Lynch syndrome
What is the CpG island methylation [CIMP] path of colon carcinogenesis? What type of polyp?
DNA methylation inhibits key gene expression
associated with sessile serrated polyps
What is most common symptom of colon cancer?
no symptoms at all!
What is presentation when colon cancer becomes symptomatic?
- change in nature of stool –> red or black; thinner
- ab cramps
- unexplained weight loss
- loss of appetite
- low blood count [anemia]
What are signs of colon cancer on physical exam?
- ab mess, tenderness, distension
- enlarged liver [if met]
- abnormal rectal exam –> mass or fecal occult blood
What are signs of rectal cancer?
tenesmus, pain, bleeding
What are signs of descending colon cancer?
signs associated with obstruction
overt bleeding
What are signs of proximal/right colon cancers?
occult bleeding
anemia
Are most colon cancers hereditary/family?
Nope – 70% are sporadic
Who is of “average” risk for colorectal cancer?
anyone > 50 yo
Who is of high risk for colorectal cancer?
- people with FAP/lynch
- IBD
- family history
- personal history
How often should you get a colonoscopy?
every 10 years
How is familial adenomatous polyposis inherited?
autosomal dominant
What are clinical feat of familiar adenomatous polyposis?
- hundreds - thousands of colorectal adenomas
- upper GI polyps
What is the mutation in FAP?
mutation in APC gene on chr 5
What is risk of developing colorectal cancer if you have familial adenomatous polyposis?
100%
What is gardner syndrome?
have FAP AND osteomas, soft tissue tumors, congenital hypertrophy of retinal pigment epithelium
What is turcot syndrome?
have FAP AND malignant brain medulloblastoma, duodenal adenocarcinoma, hepatoblastoma, thyroid carcinoma
what is normal activity of APC gene?
lives in cytoplasm; sends B-catenin into destruction path and keeps it out of the nucleus to minimize cellular proliferation and make sure apoptosis occurs
mutated –> increased proliferation and decreased apoptosis
How do you diagnose FAP?
colonoscopy
What is treatment for FAP?
prophylactic proctocolectomy
What is inheritance of lynch syndrome?
autosomal dominant mutation of DNA mismatch repair gene
What percent of people with lynch get CRC?
80%
Where are cancers from lynch usually located?
proximal colon
What is typical histology of lynch carcinoma?
signet ring cell
mucinous
medullary
infiltrating lymphocytes
What extra-intestinal cancers associated wtih lynch?
- endometrium
- GU tract
- small bowel
- brain [glioblastoma]
- stomach
- ovary
- pancreas
What is amsterdam criteria for lynch?
- 3 members affected by one of the lynch-associated cancers
- 2 or more generations
- 1 person affected under age 50
