Bad Cancer

Question 1

What is the most common cancer in males and females?

Answer 1

Lung cancer

Question 2

What is the second most common cancer in males?

Answer 2

CRC

Question 3

What is the second most common cancer in females?

Answer 3

Breast

Question 4

What is the third most common cancer in females?

Answer 4

CRC

Question 5

What influences the development of CRC?

Answer 5

Diet

• meat and increased dietary fat increases risk
• fruit, veg, folate intake decrease risk

Question 6

What are the therapies for CRC?

Answer 6

Surgery (almost all patients)
Chemotherapy - 5-FU
Radiotherapy

Question 7

What is the common metastatic location for CRC?

Answer 7

The liver

Question 8

Which lifestyles have a higher chance of developing CRC?

Answer 8

Western lifestyle

Question 9

If you eat meat regularly, how much does your chances of developing CRC increase?

Answer 9

68%

Question 10

If you red eat meat regularly, how much does your chances of developing CRC increase?

Answer 10

~130%

Question 11

If you smoke regularly, how much does your chances of developing CRC increase?

Answer 11

~50%

Question 12

What carcinogens are found at high levels in cooked meats?

Answer 12

Heterocyclic amine

Question 13

What does marinading your meat cause?

Answer 13

A decrease in heterocyclic amine carcinogens

Question 14

Give an example of a heterocyclic amine carcinogen

Answer 14

PhIP

Question 15

How does PhIP induce cancer?

Answer 15

It is metabolised by the cytochrome P450, CYP1A2 -> addition of a hydroxyl group -> very reactive and reacts with DNA

Question 16

How can you investigate the functioning of P450 enzymes?

Answer 16

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

Question 17

How does smoking cause cancer?

Answer 17

The inert protein is metabolised by the P450 enzymes continuously until it has lots of functional groups and causes DNA damage

Question 18

What protects us against smoking?

Answer 18

Enzyme such as glutathione-S-transferases which detect the protein with lots of functional groups and releases glutathione

Question 19

What is glutathione?

Answer 19

A cytoprotective compound

Question 20

What does glutathiones structure consist of?

Answer 20

Glycine
Cysteine
Glutamic acid

Question 21

Name 2 polymorphisms of glutathione-S-transferases

Answer 21

GSTM1

GSTT1

Question 22

Name two compounds which increases carcinogen activation

Answer 22

CYP1A1

CYP2C

Question 23

Name 2 compounds which reduce detoxification of carcinogens?

Answer 23

GSTM1

GSTM2

Question 24

Name 2 protective alleles

Answer 24

GSTT1

GSTP1

Question 25

When APC binds to beta-catenin, what does it induce?

Answer 25

Degradation of beta-catenin

Question 26

What happens if APC is not bound to beta-canenin?

Answer 26

beta-catenin accumulates and enters the nucleus and binds to T-cell factor -> transcription of genes and cell division

Question 27

Why is beta-catenin likely to be mutated?

Answer 27

Since it is a large protein

Question 28

Where are intestinal cells created?

Answer 28

At the bottom of the crypt where the stem cells are

Question 29

How do mutations in APC or beta-catenin form the polyp?

Answer 29

get a progenitor-like phenotype and accumulate | They are unable to continue outward migration

Question 30

How many CRC are APC mutant?

Answer 30

~70%

Question 31

What happens if you get a mutation in familial adenomateous polyposis (FAP)?

Answer 31

Get familial cancer syndrome | They form 100s/1000s of polyps in their colons and therefore have a large chance of developing cancer

Question 32

What commonly happens to FAP mutated patients as a preventative measure?

Answer 32

Have a large part of their bowel removed

Question 33

What cancer most commonly has p53 mutations?

Answer 33

Ovarian

Question 34

where do p53 mutations occur?

Answer 34

In hotspot regions

Question 35

What cancers typically have Ras mutations?

Answer 35

CRC Pancreatic cancer NSCLC

Question 36

What cancers typically have Raf mutations?

Answer 36

Melanomas CRC Esophageal Ovarian

Question 37

What codon of Ras is highly mutated?

Answer 37

13

Question 38

Are APC, p53 and Kras mutations all needed in CRC?

Answer 38

No, any one of them or combinations of any of them can cause cancer

Question 39

When do Kras mutations commonly occur in CRC?

Answer 39

Later on in CRC development (Duke's C)

Question 40

What is Kras mutations associated with?

Answer 40

Poor survival

Question 41

What monoclonal antibody targets EGFR?

Answer 41

Cetuximab