Flashcards in 03a: Colon Deck (62):
Lifetime risk of colon cancer is (X)%
X = 5
Lifetime risk of colon adenoma is (X)%
X = 60
Which behavioral trends have led to the (increase/decrease) in colon cancer (incidence/mortality)?
1. Decrease smoking
2. Improved diet/exercise
T/F: an emigrating population acquires the colon cancer risk of the new environment
True - variation in geographic incidence may be related to diet
List the modifiable factors that increase risk for colorectal cancer
1. Red and processed meat intake
3. Smoking and EtOH
4. DM II
List the modifiable factors that decrease risk for colorectal cancer
1. Physical activity
3. Hormone replacement Rx
4. Dairy/Ca, folate
T/F: about 35-40% of colorectal cancer cases are sporadic
False - 75%
Classic Familial Adenomatous Polyposis: risk of colorectal cancer approaches 100% by age (X). Caused by (Y) gene mutation.
X = 40
Y = APC (chrom 5)
Patient is 25 years old with multiple (over 100) colorectal adenomas. Which genetic disease is he likely to have? What’s the mode of inheritance?
Classic FAP; autosomal dominant
(FAP/AFAP) presents with adenomas that are predominantly right-sided. What’s the mean age at which these polyps are seen?
T/F: both FAP and AFAP are cause by genetic mutation in APC
MUTYH-associated polyposis mimics (X) disease phenotypically but has mutation in (Y)
X = FAP
Y = MUTYH (base-excision repair)
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) aka (X) Syndrome: which age of onset? And predominance of cancer at which site?
X = Lynch
40 yo or under
T/F: HNPCC results in multiple primary cancers (colorectal and extracolonic).
HNPCC: mutation in which genes?
DNA mismatch repair (MLH1,2, MSH6, PMS2)
List the two sequences of natural progression to colorectal cancer. What percent of CRC has followed each of these paths?
1. Adenoma-Carcinoma sequence (80%)
2. Serrated Adenoma Path (20%)
How long (timeline) is the Adenoma-Carcinoma sequence for colorectal cancer? List the steps
Small adenoma, large adenoma, HG dysplasia, invasive cancer, metastasis
How long (timeline) is the Serrated Adenoma pathway for colorectal cancer? List the steps
Microvesicular Hyperplasia, sessile/serrated adenoma/polyp, serrated adenoma, serrated cancer, metastasis
Individuals with one first-degree relative affected by CRC before age 60 have an (X)-fold increased lifetime risk of developing CRC. The risk applies/begins when they’re (older/younger/same age) as relative.
X = 2-3
Younger (10 y younger)
List the Amsterdam II criteria for (X) disease.
X = HNPCC
1. 3+ relatives with HNPCC associated cancer
2. 2+ generations of CRC
3. 1+ case before age 50
T/F: 95% of colorectal cancers are adenocarcinomas
Diagnostic method of choice for CRC
How might a CBC be helpful in diagnosing or verifying CRC?
Fe deficiency anemia (Sx of CRC in cecum)
CRC: best imaging study for detecting intra-abdominal spread of disease
CRC: Endoscopic ultrasound useful in assessing
depth of invasion and local lymph node status for rectal cancers
Carcinoembryonic antigen (CEA) serum levels can be used to monitor recurrence of (X) cancer after curative surgery
X = colorectal
T/F: Chemotherapy for advanced colorectal cancer (Stage IV) has proven incredibly successful.
False - v disappointing
Which type of therapy is recommended for Dukes’ C (node-positive) colon cancers?
Chemo (alone or with radiation) given post-op after curative resection
Which type of therapy is recommended for Dukes’ B2 and C rectal cancers?
1. Curative surgery
2. Chemo with high dose pre- and/or post-op radiation
Pt with no FHx of CRC: when do you start screening and how often by colonoscopy?
Average risk patient: how often do you screen with flexible sigmoidoscopy?
Every 5 y OR
every 10 y with anual FIT (fecal immunochem test)
CRC screening: CT colonography can be used every (X) years or barium enema every (Y) years
X = Y = 5
36 y.o. Pt has older brother and father with PHx of CRC. Brother got it around 55 y.o. and dad at 60 y.o. How often do you screen your patient, and starting at what age?
Every 5 y (colonoscopy)
beginning at age 45 y.o. (10y before youngest affected relative)
Your 25 y.o. patient meets the Amsterdam II criteria, but refuses genetic testing. What are the screening criteria for CRC?
Assume she's positive for HNPCC - follow those guidelines;
Colonoscopy every 1-2y starting now (age 25) and then yearly after age 40
Patient with FAP - CRC screening criteria:
Flex sigmoidoscopy yearly beginning at puberty
Patient with AFAP - CRC screening criteria:
Colonoscopy every 1-2y beginning at age 25
MUTYH polyposis screening criteria
(Same as AFAP):
Colonoscopy every 1-2y beginning at age 25
The Classical APC, aka (X), pathway originates with mutation in (one/both) alleles of (Y) gene in which cell?
X = MSS (microsatellite stable)
Y = APC
Stem cell in colonic mucosal crypt
CRC: APC mutation causes (X) cell to produce APC protein that has which issues?
X = stem cell (in colonic mucosal crypt)
Truncated - loses critical function of sequestering beta-catenin
CRC: beta-catenin protein, normally (stimulated/inhibited) by (X), has which roles?
Inhibited; X = APC
1. Cell-cell adhesion
2. Component of growth-promoting nuclear TF
APC pathway for CRC: the earliest lesion formed is termed (X).
X = aberrant crypt focus OR microadenoma
APC pathway for CRC: from a microadenoma, the next step is formation of (X). These small adenomas frequently contain up-regulated (Y) enzyme, which inhibits apoptosis.
X = tubular adenomas
Y = COX2
APC pathway for CRC: Mutation of (X) (oncogene/suppressor) frequently associated with large tubulovillous or villous adenomas.
X = KRAS
T/F: All colonic adenomas show at least low-grade dysplasia
APC pathway for CRC: (X) mutation has been associated with the step from low- to high-grade dysplasia
X = p53
Endpoint colorectal adenocarcinoma of APC pathway characterized by:
Chromosomal instability (but microsatellite stable) - chromosome breaks, losses, duplications, gene deletions
CRC Serrated Polyp Path: originates with mutation of (X) in which cell?
X = BRAF or KRAS (oncogene belonging to RAS-RAF-MAP kinase path)
Crypt stem cell
T/F: transformed appearance of cells in early part of Serrated Polyp Path is nearly identical to those of APC path.
False - distinct appearance of senescence (as opposed to dysplastic aberrant crypt foci in APC path)
T/F: Some BRAF/KRAS mutation in early polyps of serrated path pose no clinical risk of progression
True - if constrained by senescence
CRC Serrated Polyp Path: following BRAF/KRAS mutation, list the two variants of serrated polyps that are immediate precursors to cancer.
1. Sessile Serrated Adenoma
2. Traditional Serrated Adenoma
Sessile serrated adenomas are located mainly in (prox/distal) colon with (flat/serrated) appearance.
Proximal; flat (sessile)
T/F: Sessile serrated adenomas must pass through senescence process prior to progression to dysplasia/cancer.
False - can bypass senescence
CRC Serrated Polyp Path: (X) precursor to colon cancer can bypass senescence and progress by which process?
X = sessile serrated adenoma
Epigenetic CpG island methylation (inactivates tumor suppressor genes and mismatch repair gene hMLH1)
Serrated polyp path: Inactivation of (X) gene by CpG island methylation is crucial to progression of (Y) adenoma to colon cancer.
X = hMLH1
Y = sessile serrated
T/F: Sessile serrated cancers are microsatellite instable.
T/F: Serrated pathway cancers present in older adults, compared to APC path, with poor prognosis.
False - present in older adults, but good prognosis
Traditional serrated adenomas are located mainly in (prox/distal) colon with (flat/serrated) appearance.
T/F: Traditional serrated cancers are microsatellite instable.
False - MSS
Which colonic adenomas have pronounced eosinophilia of epithelial cells?
Traditional Serrated Adenomas have (KRAS/BRAF) mutation.
Either (but BRAF more highly aggressive/incurable)
Traditional Serrated Adenomas: what are the important engines of progression to cancer?
1. CpG island methylation
2. Chromosomal instability