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2 Pathological Processes > 15 Neoplasia 3 > Flashcards

15 Neoplasia 3 Flashcards

1
Q

Define Carcinogenesis.

A

causes of cancer

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2
Q

What are the INTRINSIC factors which account for cancer risk? (in general terms)

A
  • Heredity
  • Age
  • Sex (hormonal)
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3
Q

What are the EXTRINSIC factors which account for cancer risk?(in general terms)

A
  • Environment
  • Behaviour
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4
Q

What are the 5 leading behavioural and dietary risks that account for 30% of cancer deaths?

A
  1. Smoking
  2. Alcohol
  3. Not enough fruit and veg
  4. Lack of physical activity
  5. High BMI
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5
Q

What % of cancer deaths deaths does tobacco smoke account for?

A

about 25%

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6
Q

What are the 3 main categories of EXTRINSIC carcinogens?

A
  1. Chemicals 2.Radiation 3. Infections
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7
Q

With relation to carcinogens, what factors affect the risk of cancer/cancer itself? (3)

A

1) Time between exposure and onset of malignancy
2) Total dosage
3) Organ (some carcinogens have organ specificity)

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8
Q

What two processes need to occur in sequence for chemical carcinogenesis to occur?

A

Initiation then promotion (some carcinogens= initiators, some =promoters)

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9
Q

What did the ‘Ames test’ show?

A

Initiators= mutagens

Promoters= cause prolonged proliferation in target tissues

–> all cause monoclonal expansion of mutant cells

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10
Q

How are chemical carcinogens classified?

A
  • Polycyclic aromatic carcinogens
  • Aromatic amines
  • N-nitrosocompounds
  • Alkylating agents
  • Diverse natural products e.g. asbestos
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11
Q

What is a ‘complete carcinogen’?

A

Carcinogen which acts as initiator and promoter

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12
Q

What are pro-carcinogens?

A

chemicals- converted to carcinogens by P450 enzyme

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13
Q

How can radiation damage DNA?

A

DIRECTLY / INDIRECTLY- generates free radicals. Ionising radiation- damages DNA bases, causes single and double strand breaks

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14
Q

Apart from UV radiation, what is the other main source of radiation people are exposed to?

A

Natural background radiation from earth’s crust- radon

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15
Q

How are some infections directly carcinogenic?

A

Affect genes that control cell growth

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16
Q

How are some infections indirectly carcinogenic?

A

Cause chronic tissue injury- resulting regeneration

17
Q

Give examples of infections which can be carcinogenic and how?

A

1) HPV- human papilloma virus-cervical carcinoma. Inhibits p53 and pRB function (DIRECT) 2) Hep B and C- chronic cell injury 3) Helicobacter pylori- chronic gastric inflammation 4)Parasitic flukes- inflammation in bile ducts 5)HIV- lowering immunity- allows potentially carcinogenic infections to occur

18
Q

Give an example of an inherited predisposition to a malignancy.

A

Retinoblastoma- through germline mutations.

19
Q

What is Knudson’s ‘Two hit hypothesis’?

A

=explains differences between familial tumour patterns and sporadic tumours (e.g. with retinoblastoma). FAMILIAL cancers- first mutation is in gremlin (all cells in body), second is somatic mutation SPORADIC cancers- requires 2 somatic mutations

20
Q

What types of genes does Knudson’s ‘Two hit hypothesis’ refer to?

A

Tumour supressor genes (only require 1 oncogene to favour neoplastic growth (i.e. proto-oncogene mutation))

21
Q

Give an example of an oncogene and how is causes neoplasm?

A

Mutant RAS encodes small G protein- pushes cell past restriction point. Mutant RAS= always active.

22
Q

Give and example of a tumour suppressor gene.

A

RB gene

23
Q

What is Xeroderma pigmentosum (XP)?

A

Autosomal recessive disease- mutation in DNA NUCLEOTIDE EXCISION REPAIR (NER) (caretaker gene)-patients= v sensitive to UV, develop skin cancer- young age

24
Q

What is HNPCC

A

Hereditary non-polyposis colon cancer syndrome- associated w./ colon carcinoma- (germline mutation)

25
Q

What do the BRCA1 and BRCA2 genes do and what might mutations in these genes predispose someone to?

A

They repair double strand DNA breaks

Familial breast carcinoma

26
Q

What is genetic instability?

A

Accelerated mutation rate in malignant neoplasms

27
Q

What do we call the tumour suppressor genes that maintain ‘genetic stability’?

A

Caretaker genes

28
Q

What is cancer ‘progression’?

A

Steady accumulation- multiple mutations.

29
Q

Outline an example of an adenoma-carcinoma sequence.

A

COLON CARCINOMA 1. Colonic adenoma 2. Primary carcinoma 3. Metastatic carcinoma (acculmulation of mutations)

30
Q

What are the 6 hallmarks of cancer? (exhibited by a malignant neoplasm)

A

1) SELF SUFFICIENCY in growth signals
2) RESISTANCE to growth stop signals
3) NO LIMIT to division (IMMORTALISATION)
4) SUSTAINED ABILITY -produce new blood vessels (ANGIOGENESIS)
5) APOPTOSIS RESISTANCE
6) ABILITY to invade and produce metastases

(hallmarks 1-5= relevant to benign and malignant neoplasms)

31
Q

Give an example of an enabling feature of malignant neoplasms.

A

Genetic instability

32
Q

In what % of cancers are inherited mutations in the germline present?

A

5%

2 Pathological Processes (12 decks)

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