Bad Cancer Flashcards
What is the most common cancer in males and females?
Lung cancer
What is the second most common cancer in males?
CRC
What is the second most common cancer in females?
Breast
What is the third most common cancer in females?
CRC
What influences the development of CRC?
Diet
- meat and increased dietary fat increases risk
- fruit, veg, folate intake decrease risk
What are the therapies for CRC?
Surgery (almost all patients)
Chemotherapy - 5-FU
Radiotherapy
What is the common metastatic location for CRC?
The liver
Which lifestyles have a higher chance of developing CRC?
Western lifestyle
If you eat meat regularly, how much does your chances of developing CRC increase?
68%
If you red eat meat regularly, how much does your chances of developing CRC increase?
~130%
If you smoke regularly, how much does your chances of developing CRC increase?
~50%
What carcinogens are found at high levels in cooked meats?
Heterocyclic amine
What does marinading your meat cause?
A decrease in heterocyclic amine carcinogens
Give an example of a heterocyclic amine carcinogen
PhIP
How does PhIP induce cancer?
It is metabolised by the cytochrome P450, CYP1A2 -> addition of a hydroxyl group -> very reactive and reacts with DNA
How can you investigate the functioning of P450 enzymes?
Genotyping by ‘Tagman’
- take a finger print and do a PCR -> split them into groups, those with functioning enzyme, those with an inactive form and a heterozygous group which have reduced activity of enzyme
How does smoking cause cancer?
The inert protein is metabolised by the P450 enzymes continuously until it has lots of functional groups and causes DNA damage
What protects us against smoking?
Enzyme such as glutathione-S-transferases which detect the protein with lots of functional groups and releases glutathione
What is glutathione?
A cytoprotective compound
What does glutathiones structure consist of?
Glycine
Cysteine
Glutamic acid
Name 2 polymorphisms of glutathione-S-transferases
GSTM1
GSTT1
Name two compounds which increases carcinogen activation
CYP1A1
CYP2C
Name 2 compounds which reduce detoxification of carcinogens?
GSTM1
GSTM2
Name 2 protective alleles
GSTT1
GSTP1
When APC binds to beta-catenin, what does it induce?
Degradation of beta-catenin
What happens if APC is not bound to beta-canenin?
beta-catenin accumulates and enters the nucleus and binds to T-cell factor -> transcription of genes and cell division
Why is beta-catenin likely to be mutated?
Since it is a large protein
Where are intestinal cells created?
At the bottom of the crypt where the stem cells are
How do mutations in APC or beta-catenin form the polyp?
get a progenitor-like phenotype and accumulate
They are unable to continue outward migration
How many CRC are APC mutant?
~70%
What happens if you get a mutation in familial adenomateous polyposis (FAP)?
Get familial cancer syndrome
They form 100s/1000s of polyps in their colons and therefore have a large chance of developing cancer
What commonly happens to FAP mutated patients as a preventative measure?
Have a large part of their bowel removed
What cancer most commonly has p53 mutations?
Ovarian
where do p53 mutations occur?
In hotspot regions
What cancers typically have Ras mutations?
CRC
Pancreatic cancer
NSCLC
What cancers typically have Raf mutations?
Melanomas
CRC
Esophageal
Ovarian
What codon of Ras is highly mutated?
13
Are APC, p53 and Kras mutations all needed in CRC?
No, any one of them or combinations of any of them can cause cancer
When do Kras mutations commonly occur in CRC?
Later on in CRC development (Duke’s C)
What is Kras mutations associated with?
Poor survival
What monoclonal antibody targets EGFR?
Cetuximab
