Neoplasia 3

Question 1

How much do environmental factors contribute to cancer risk?

Answer 1

85 %

Question 2

What are the 5 leading behavioural factors that increase risk of cancer?

Answer 2

1. high BMI
2. low fruit and veg intake
3. lack of physical activity
4. alcohol use
5. tobacco use

Question 3

What are the 3 main categories of extrinsic carcinogens

Answer 3

1. chemicals
2. radiation
3. infection

Question 4

What 3 lessons do malignant neoplasms caused by 2-napthylamine teach use

Answer 4

1) there is a long delay between carcinogen exposure and neoplasm onset
2) risk of cancer depends on total carcinogen dosage
3) there is sometimes organ specificity for particular carcinogens

Question 5

Explain how to Ames test works

Answer 5

• A strain of salmonella that requires histadine to grow is mixed with rat liver extract
• possible mutagen added to sample and spread on media with minimal histadine
• strain with no possible mutagen added as a control plate
• if the substance is mutagenic, will see a high number of revertants that grow. Shows it has caused a mutation

Question 6

What are pro-carcinogens?

Answer 6

Chemicals that only become carcinogens by CYP450 enzyme conversion in the liver

Question 7

What are complete carcinogens?

Answer 7

Carcinogens that acts as both initiators AND promotors

Question 8

Why is rat liver extract required in the Ames test?

Answer 8

To convert any possible pro-carcinogens to carcinogens

Question 9

How can radiation directly damage DNA?

Answer 9

• alter bases
• induce single/ double stranded breaks

Question 10

How can radiation cause indirect DNA damage?

Answer 10

By crashing into H20 to produce FREE RADICALS

Question 11

What is the most important type of radiation and why?

Answer 11

UV exposure as we’re exposed to it daily

Question 12

What are the 2 main types of ionising radiation we are exposed to?

Answer 12

• radon gas
• medical tests (X-Ray/CT)

Question 13

How does HPV cause cervical cancer?

Answer 13

It expresses proteins E6 and E7

• E6 inhibits p53
• E7 inhibits Rb protein

Question 14

How do Hep B and C cause cancer?

Answer 14

Indirect carcinogens that cause chronic liver injury and regeneration

Question 15

How is HIV involved in cancer?

Answer 15

Lowers host immunity allowing other potentially carcinogenic infections to occur

Question 16

How does Heliobacter pylori increase risk for gastric cancer?

Answer 16

Causes chronic gastric inflammation, increasing risk of carcinoma

Question 17

How do parasitic flukes lead to bladder carcinoma?

Answer 17

Cause inflammation of bile ducts and bladder mucosa

Question 18

Explain Knudson’s two hit hypothesis

Answer 18

2 mutations are required in the same cell for cancer to occur

Question 19

Explain the difference between the number of mutations required for tumour suppressor genes and proto oncogene to cause cancer

Answer 19

Tumour suppressor gene - both alleles need a mutation

Proto oncogene- only 1 allele needs to be mutated

Question 20

Explain how mutations in RAS can cause neoplasia?

Answer 20

Normal RAS encodes a G protein that causes the cell to move past the restriction point when activated

In mutation - RAS the protein will always be active so is constantly driving cell proliferation past the restriction point

Question 21

In what proportion of malignant neoplasms is the RAS gene mutated?

Answer 21

1/3

Question 22

How does RB gene mutation cause neoplasia?

Answer 22

Normal Rb gene acts as a inhibitor of the cell cycle by acting on the restriction point

Both Rb alleles need mutations to allow cells to pass through the restriction point.

Question 23

What are caretaker genes?

Answer 23

Genes that prevent the accumulation of DNA damage by repairing defects

Question 24

Explain how BRCA1 and BRCA2 is associated with familial breast cancer

Answer 24

Normal BRCA1 and BRCA2 repair DNA double strand breaks

Mutations mean repair isn’t fixed which drives proliferation

Question 25

What is HNPCC (hereditary non-polypsosis colon cancer)

Answer 25

• Autosomal dominant condition
• Germline mutation affects several DNA mismatch repair genes

Question 26

How is xeroderma pigmentosum caused?

Answer 26

Mutations in any of the 7 genes that affect DNA nucleotide excision repair

Question 27

What is the adenoma-carcinoma sequence?

Answer 27

Carcinomas usually arise from adenomas that have accumulated more mutations

Question 28

How many mutations are needed for a fully evolved malignant neoplasms to occur

Answer 28

Approximately 10 or less

Question 29

What are the 6 hallmarks of cancer

Answer 29

1) self-sufficiency in growth signals
2) resistance to growth stop signals
3) grow indefinitely (cell immortalisation)
4) angiogenesis
5) resistance to apoptosis
6) ability to invade and produce new metastasis

Question 30

Describe the sequence of events that are involved in the model of cancer pathogenesis

Answer 30

1) somatic cells exposed to environmental carcinogens that cause an initial mutation
2) additional carcinogens act as promoters which cause sustained proliferation
3) some of the mutations may be in proto oncogenes or tumour suppressor genes
4) cells acquire further activation of proto oncogenes/ inactivation of tumour suppressors known as progression
5) after many years of progression the cells acquire mutations that produce the hallmarks of cancer

Question 31

What % of cancer risk due to extrinsic factors is potentially avoidable?

Answer 31

85%

Question 32

How does t-cell lymphoma occur?

Answer 32

Viral infection

Question 33

What malignancy is associated with Paget’s disease?

Answer 33

Osteosarcoma

Question 34

What kind of bladder cancer does schistosomiasis cause?

Answer 34

Squamous cell carcinoma