Carcinogenesis (UNFINISHED)

Question 1

What are the 6 main categories of human carcinogens?

Answer 1

• chemicals
• infectious agents
• radiation
• minerals
• physiological
• chronic inflammation

Question 2

What does genotoxic mean?

Answer 2

can chemically modify or damage DNA (initiators)

Question 3

What does it mean if a carcinogen in ‘complete’?

Answer 3

it can initiate and promote

Question 4

Give an example of a complete carcinogen?

Answer 4

UV light

Question 5

What does initiation require?

Answer 5

• chemical modification of DNA

- replication of modified DNA and mis-incorporation of DNA polymerase

Question 6

What are the 2 main functions of promoters?

Answer 6

• stimulate 2 rounds of DNA replication necessary for mutation fixation
• stimulate clonal expansion of mutated cells

Question 7

What is the most common TSG inactivation event?

Answer 7

gene promoters can become abnoramlly methylated

Question 8

What is the consequence of mutations in oncogenes?

Answer 8

gain of function

Question 9

What is the consequence of mutations of TSGs (tumour suppressor genes)?

Answer 9

loss of function

Question 10

What common mutations occur in oncogenes?

Answer 10

base pair substitutions, amplification, translocations, inversions

Question 11

Are oxygen radicals, nitrosomines, UV light and ionising radiation examples of direct acting carcinogens or procarcinogens?

Answer 11

direct acting

Question 12

Define procarcinogen

Answer 12

require enzymatic (metabolic) activation before they react with DNA

Question 13

What can inherited defects in the nucleotide-excision repair pathway lead to?

Answer 13

Xeroderma pigmentosum - group of rare autosomal recessive inherited disorders characterised by extreme skin sensitivity to UV light, high frequency of skin cancer and abnormal pigmentations

Question 14

What is ataxia telangiectasia?

Answer 14

an autosomal recessive disorder due to inherited defects in ATM gene (involved in recombinational repair pathway) and leads to 100-fold increase in rate of cancer

Question 15

What is the common cause of HNPCC?

Answer 15

,mutations in one of the several mismatch-repair genes

Question 16

How many carcinogens can be identified in tobacco smoke?

Answer 16

19

Question 17

What is the active form of propcarcinogen in alcohol?

Answer 17

acetaldehyde

Question 18

What are all of the strongest risk factors for breast cancer associated with increased exposure to?

Answer 18

oestrogen

Question 19

How is chronic inflammation linked to cancer?

Answer 19

• DNA damage from release of free radicals by immune cells = INITIATION
• Growth factor induced cell division to repair tissue damage = PROMOTION

Question 20

What is the role of caretaker genes?

Answer 20

maintain genetic stability by replacing damaged DNA and replication errors

Question 21

What is the role of gatekeeper genes?

Answer 21

• negative regulation of cell cycle proliferation
• positive regulation of apoptosis
• positive regulation of cell differentiation

Question 22

Mutations of which gene are associated with retinoblastoma?

Answer 22

RB1 (gatekeeper)

Question 23

Mutations of which gene are associated with Li-Fraumeni?

Answer 23

p53 (gatekeeper/caretaker)

Question 24

Mutations of which gene are associated with familial adenomatous polyposis?

Answer 24

APC (gatekeeper)

Question 25

Mutations of which gene are associated with familial breast cancer?

Answer 25

BRCA1, BRCA2 (caretakers)

Question 26

Mutations of which genes are associated with HNPCC?

Answer 26

hMLH1, hMSH2 (caretaker)

Question 27

What is the function of proto-oncogenes?

Answer 27

promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis

Question 28

For oncogenes, is the mutated or normal gene dominant?

Answer 28

mutated gene is dominant, therefore only 1 copy of the gene needs to be activated to induce gain in function

Question 29

What are the three main mechanisms of oncogene activation?

Answer 29

transolcation, point mutation and amplification

Question 30

What ae the 6 main characteristics of cancer cells?

Answer 30

- self sufficiency in growth signals - insensitivity to antigrowth signals - tissue invasion and metastasis - limitless potential for replication - sustained angiogenesis - evading apoptosis

Question 31

Inactivation of which gene is common in tumours resulting in resistance to negative growth regulation?

Answer 31

Rb gene

Question 32

What gene plays the key role on apoptosis and inherited mutations of this gene causes what familial cancer syndrome?

Answer 32

TP53 - Li Fraumeni

Question 33

Which adhesion molecuel is commonly abscent from tumours?

Answer 33

E-cadherin