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Mechanisms of Disease > Carcinogenesis (UNFINISHED) > Flashcards

Carcinogenesis (UNFINISHED) Flashcards

1
Q

What are the 6 main categories of human carcinogens?

A
  • chemicals
  • infectious agents
  • radiation
  • minerals
  • physiological
  • chronic inflammation
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2
Q

What does genotoxic mean?

A

can chemically modify or damage DNA (initiators)

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3
Q

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

A

it can initiate and promote

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4
Q

Give an example of a complete carcinogen?

A

UV light

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5
Q

What does initiation require?

A
  • chemical modification of DNA

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

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6
Q

What are the 2 main functions of promoters?

A
  • stimulate 2 rounds of DNA replication necessary for mutation fixation
  • stimulate clonal expansion of mutated cells
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7
Q

What is the most common TSG inactivation event?

A

gene promoters can become abnoramlly methylated

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8
Q

What is the consequence of mutations in oncogenes?

A

gain of function

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9
Q

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

A

loss of function

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10
Q

What common mutations occur in oncogenes?

A

base pair substitutions, amplification, translocations, inversions

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11
Q

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

A

direct acting

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12
Q

Define procarcinogen

A

require enzymatic (metabolic) activation before they react with DNA

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13
Q

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

A

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

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14
Q

What is ataxia telangiectasia?

A

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

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15
Q

What is the common cause of HNPCC?

A

,mutations in one of the several mismatch-repair genes

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16
Q

How many carcinogens can be identified in tobacco smoke?

A

19

17
Q

What is the active form of propcarcinogen in alcohol?

A

acetaldehyde

18
Q

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

A

oestrogen

19
Q

How is chronic inflammation linked to cancer?

A
  • DNA damage from release of free radicals by immune cells = INITIATION
  • Growth factor induced cell division to repair tissue damage = PROMOTION
20
Q

What is the role of caretaker genes?

A

maintain genetic stability by replacing damaged DNA and replication errors

21
Q

What is the role of gatekeeper genes?

A
  • negative regulation of cell cycle proliferation
  • positive regulation of apoptosis
  • positive regulation of cell differentiation
22
Q

Mutations of which gene are associated with retinoblastoma?

A

RB1 (gatekeeper)

23
Q

Mutations of which gene are associated with Li-Fraumeni?

A

p53 (gatekeeper/caretaker)

24
Q

Mutations of which gene are associated with familial adenomatous polyposis?

A

APC (gatekeeper)

25
Q

Mutations of which gene are associated with familial breast cancer?

A

BRCA1, BRCA2 (caretakers)

26
Q

Mutations of which genes are associated with HNPCC?

A

hMLH1, hMSH2 (caretaker)

27
Q

What is the function of proto-oncogenes?

A

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

28
Q

For oncogenes, is the mutated or normal gene dominant?

A

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

29
Q

What are the three main mechanisms of oncogene activation?

A

transolcation, point mutation and amplification

30
Q

What ae the 6 main characteristics of cancer cells?

A
  • self sufficiency in growth signals
  • insensitivity to antigrowth signals
  • tissue invasion and metastasis
  • limitless potential for replication
  • sustained angiogenesis
  • evading apoptosis
31
Q

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

A

Rb gene

32
Q

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

A

TP53 - Li Fraumeni

33
Q

Which adhesion molecuel is commonly abscent from tumours?

A

E-cadherin

Mechanisms of Disease (16 decks)

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