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Pathological Processes > 9. Neoplasia 3 > Flashcards

9. Neoplasia 3 Flashcards

1
Q

What are the 5 leading behavioural and dietary risks associated with cancer?

A 
high BMI
low fruit and veg intake 
low physical activity
smoking
alcohol
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2
Q

What are the 3 categories of extrinsic factors that are cancer risks?

A

Infection
Chemicals
Radiation

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3
Q

What intrinsic factors are linked to cancer?

A

Age
Sex
Hereditary

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4
Q

What industrial carcinogen was used in dye manufacturing and what cancer did it cause?

A

2-napthylamine, bladder cancer

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5
Q

What 3 things did 2-napthylamine show?

A
  1. Time delay between carcinogen exposure and development
  2. Risk depends on total carcinogen dosage
  3. Carcinogens can be tissue specific
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6
Q

What did the Ames test show?

A

Initiators are mutagens while promoters cause proliferation in target tissues

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7
Q

What examples are there of mutagenic chemicals?

A 
Alkylating agents
Aromatic amines
N-nitroso compounds
Natural products - asbestos
Polycyclic aromatic carbons
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8
Q

What are pro carcinogens?

A

Chemicals that are converted to carcinogens in the liver by CYP 450 enzymes

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9
Q

What are complete carcinogens?

A

Carcinogens that act both as a promotor and an initiator

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10
Q

How can radiation cause cancer?

A

Indirectly through free radial generation

Directly through damage to bases and causing single stranded and double stranded DNA breaks

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11
Q

What are the most common forms of radiation that people are exposed to?

A

Radon in earths crust
UV radiation from sunlight
Medical tests

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12
Q

What 2 ways can infections cause cancer?

A

Directly by affecting genes that control cell growth
Indirectly by causing chronic damage and regeneration which acts either as a promotor or causes new mutations through replication errors.

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13
Q

Which infection causes cancer directly?

A

HPV - cervical cancer

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14
Q

How does HPV directly cause cancer ?

A

Produces E6 and E7 proteins.
E6 inhibits p53
E7 inhibits pRb

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15
Q

How do Hep B and C cause cancer?

A

Indirectly by chronic liver injury and regeneration which increases accumulation of mutations.

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16
Q

What cancer do Hep B and C cause?

A

Hepatocellular carcinoma

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17
Q

How does Helicobacter pylori cause cancer?

A

Gastric inflammation causes increased risk of gastric adenocarcinoma

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18
Q

How does HIV cause cancer?

A

Indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur

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19
Q

What cancer is a HIV defining illness?

A

Kaposi’s sarcoma caused by Human herpes simplex

- purple lesions under the skin

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20
Q

What cancer was used to demonstrate the 2-hit hypothesis?

A

Retinoblastoma

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21
Q

Describe the 2 hit hypothesis of oncogenesis.

A

Mutations in TSG’s are inactivating, so mutations in both alleles are required for tumour growth.
In familial cancers, first hit is in germline mutation so only 1 somatic mutation is required to cause cancer, which is very likely.

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22
Q

What are examples of oncogenes?

A

Ras
HER-2
c-myc

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23
Q

How does Ras act as an oncogene?

A

It codes for a G-protein which causes transcription of Cyclin D, which activates CDK, causing phosphorylation of Rb and allowing constant entry to the cell cycle when it’s switched on.

24
Q

What type of genes are Rb and p53?

A

Tumour suppressor genes

25
Q

What is the role of Rb gene?

A

restrains cell proliferation by inhibiting passage through the restriction point.

26
Q

How does c-myc act as an oncogene?

A

Transcription factor for a gene that promotes cell proliferation

27
Q

How is Xeroderma pigmentosum (XP) inherited?

A

Autosomal recessive

Mutations in DNA repair genes that affect nucleotide excision repair (NER)

28
Q

What cancer are patients with XP at risk of?

A

Skin cancer - very sensitive to UV

29
Q

How is hereditary non-polyposis colon cancer (HNPCC) inherited?

A

Autosomal dominant

Germline mutations affect DNA mismatch repair genes

30
Q

What cancer is HNPCC associated with?

A

Colon carcinoma

31
Q

Which genes are associated with the inheritance of familial breast cancer?

A

BRCA1 and BRCA2

32
Q

What process are the BRCA genes important for?

A

Repair of ds DNA breaks

33
Q

What is the adeno-carcinoma sequence?

A

Colon carcinoma usually begins as a colonic adenoma which accumulates mutations to emerge as a carcinoma

34
Q

What principle does the adenocarcinoma sequence demonstrate?

A

Most malignant tumours require alterations affecting a combination of multiple TS genes and proto-oncogenes over time (decades typically) = Cancer progression

35
Q

What are the 6 hallmarks of cancer?

A
  1. Self-sufficiency in growth signals
  2. Resistance to anti-growth signals
  3. No time limit on number of times it can divide
  4. Induce angiogenesis
  5. Resist apoptosis
  6. Ability to invade and metastasise
36
Q

What is classes as an enabling characteristic of cancer?

A

Genetic instability - acceleration of mutations

37
Q

What growth factor stimulates angiogenesis?

A

VEGF

38
Q

Which medical conditions are associated with increased risk of malignancy?

A

Ulcerative colitis
Cirrhosis
Hashimotos’s thyroiditis
Chronic atrophic gastritis

39
Q

What cancer is Epstein-Barr virus associated with?

A

Burkitt’s lymphoma - infects B cells

Not common in UK as no malaria

40
Q

What cancers can be caused by asbestos?

A

Lung adenocarcinoma or mesothelioma

41
Q

What is mesothelioma?

A

Cancer of the mesothelial cells (e.g in lung pleura)

42
Q

How is asbestos thought to cause cancer?

A

A complete carcinogen - initiator and promotor

Pro-inflammatory

43
Q

What was asbestos used for?

A

Roofing, insulation, fire proofing

44
Q

Why is there an even higher increased risk of lung cancer in people who are exposed to asbestos AND smoke?

A

Carcinogens from smoke absorbed in asbestos fibres with carry them deeper into the lungs.
Smoking paralyses cilia, prevents clearance.

45
Q

How can you identify squamous cell carcinoma under a microscope?

A

Keratin production

46
Q

What do basal cell carcinomas look like?

A

Pearly, nodular, raised, rolled-edge, volcano-like

47
Q

How can you identify malignant melanoma under a microscope?

A

Melanin production visible

48
Q

What are triple negative breast cancers?

A

HER2, ER and PR negative

49
Q

What agent in cigarette smoke is carcinogenic, are they initiators or promoters?

A

Polycyclic aromatic hydrocarbons - initiators

50
Q

What types of lung cancer are associated with smoking?

A

Small cell carcinoma

Squamous cell carcinoma

51
Q

What effect does smoking have on the bronchial epithelium?

A

Causes metaplasia which can progress to squamous dysplasia and result in carcinoma in-situ and then invasive carcinoma.

52
Q

What are the 2 inherited forms of colon cancer?

A
  1. HNPCC

2. Familial adenomatous polyposis (FAP)

53
Q

What are the pathological features of FAP?

A

Patients develop thousands of colonic adenomas (polyps) that carpet mucosal surface which progress to colon cancer by 50 years old if not removed.

54
Q

How is FAP treated?

A

Prophylactic colectomy

55
Q

What gene is involved in FAP?

A

Adenomatous polyposis colon (APC) gene.

Autosomal dominant mutation of a tumour suppressor gene.

56
Q

Which germline mutation is associated with osteosarcoma?

A

RB1

Pathological Processes (12 decks)

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