Cancer as a Disease - Colorectal Cancer Flashcards
What is the 4th most common cancer
Colorectal
What is the leading cancerous cause of death
Lung
What is the second leading cancerous cause of death
Colorectal
Colon cancer corresponds to cancer between the ….
ileocecal valve up to the anus, not including the appendix.
Why are colorectal cells particularly vulnerable to cancer
High proliferation
What is a polyp
is any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc.
What are the cancer causing polyps known as
Adenomatous
What are benign and common polyps known as
- Metaplastic/Hyperplastic
What mutation causes Metaplastic/Hyperplastic polyps
K-Ras
Colonic adenoma types? Commonness? Describe each? (3)
- Tubular (test tubes) - most common >75% of the tumour is tubular
- Tubulovillous (mix of tubular and villous) 25-50% tubular and villous
- Villous (fingery things) - larger and worse >50% of the tumour is villous
AKA PEDUNCULATED or SESSILE -> Pedunculated looks like a tree, sessile looks like a thick rug
What type of cells are tubular adenomas? what features are displayed in the cell? (4)
- Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
Features of tubular adenomas? (5)
- Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Stratified or pseudostratified, no nice architecture, more purple due to higher nuclear:cytoplasm ratio, increased mitotic activity.
- Increased proliferative activity
- Reduced differentiation
- Complexity/disorganisation of architecture
Features of villous adenomas? (5)
- Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Exophytic, frond-like extensions
- Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
What type of cells are tubular adenomas?
Mucinous cells
What gene mutation causes APC
APC/FAP 5q21 gene mutation
- X% of adults have adenomas at age 50
- Y% of these become cancers if left
25%
5%
what is micro satellite instability
mismatch repair genes damage
Explain for microsatellite instability can cause cancer in the colon
Cells are dividing all the time and are bound to make mistakes- but mismatch repair genes fix them usually
If mismatch repair genes are damaged (microsatellite instability), you cannot repair DNA, so the cell loses control of growth and the risk of cancer increases
Adenoma carcinoma sequence?
- Cumulative damage to DNA
- Loss of control of cell growth
- Leads to carcinoma (often through an adenoma first)
2 main pathways of getting colon cancer?
- FAP - inactivation of APC tumour suppressor genes
- HNPCC - microsatellite instability
Places where colon cancer is low?
Japan, Mexico, Africa
Where are HCAs found and how do they contribute to cancer
found in meat cooked at high temperatures
- Cooking foods at high temperatures can release/develop mutagenic chemicals from HCAs
What lack of/excess nutrients can cause colon cancer?
lack of folate, High Fat, Low Fibre, High Red meat, Refined carbohydrates
Anti cancer foods?
- Vitamin C - ROS scavenger
- Vitamin E - ROS scavenger
- Isothiocyanates (cruciferous veg)
- Polyphenols (green tea, fruit juice)
Activate MAPK- regulates phase II detoxifying enzymes as well as other genes- reduces DNA oxidation
Clinical presentation of colorectal cancer?
- Change in bowel habit
- Rectal bleeding
- Unexplained iron deficiency anaemia The cancer bleeds
- Mucus
- Bloating
- Cramps (‘colic’)
- Weight loss
- Fatigue
Dukes staging?
DUKES A: - growth limited to wall - nodes negative DUKES B: - growth beyond muscularis propria (bowel wall) - nodes negative DUKES C1: - nodes positive - apical lymph node (LN) negative DUKES C2: - apical LN negative
What is Dukes A?
- growth limited to wall
- nodes negative
What is Dukes B?
- growth beyond muscularis propria (bowel wall)
- nodes negative
What is Dukes C1?
- nodes positive
- apical lymph node (LN) negative
What is Dukes C2?
- apical LN negative
What effect on prognosis for colon cancer does rectal bleeding as a presenting symptom have?
Improved
What effect on prognosis for colon cancer does bowel obstruction/perforation have?
Diminish
What effect on prognosis for colon cancer does preoperative serum CEA have?
Diminish with high
What effect on prognosis for colon cancer does mucinous or signet cells have?
Diminish
What effect on prognosis for colon cancer does inflammation and immunologic reaction have?
Improve
What effect on prognosis for colon cancer does location have?
Colon better than rectum
Treatment options?
basically is either chemo alone, or surgery and chemo)
Screening occurs if you have what risk factors? (6)
- Previous adenoma
- 1st Degree relative affected by colorectal cancer before the age of 45
- 2 affected first degree relatives
- Evidence of dominant familial cancer trait including colorectal, uterine, and other cancers
- UC and Crohn’s disease
- Hereditable cancer families (include other sites)
What is required for screening to be worthwhile
- Importance of the disease condition should be important in respect to the seriousness and/or frequency
- The natural history of the disease must be known in order to:
1. To identify where screening can take place
2. To enable the effects of any intervention to be assessed - Test characteristics:
simple and acceptable to the patient
sensitive and selective - The screening population should have equal access to the screening procedure.
- Cost effectiveness
When does the NHS allow screening for colorectal cancer
offered over 55 in some areas, and offered to everyone over 64
