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Year 2 EMS MoD > Carcinogenesis - Causes of Cancer > Flashcards

Carcinogenesis - Causes of Cancer Flashcards

1
Q

What sort of food causes colorectal cancer?

A

Processed meat.

-also association with red meat

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2
Q

What chemicals in rubber can cause cancer?

A
  • B-napthylamine

- 4-aminobiphenyl

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3
Q

What are the main categories of human carcinogens?

A
  • Chemicals
  • Infectious agents (e.g. HPV)
  • Radiation
  • Minerals
  • Physiological (e.g. androgens)
  • Chronic inflammation
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4
Q

What is a common factor when carcinogens cause cancer?

A

Prolonged exposure.

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5
Q

What organ does aflaxtoxin target?

A

Liver.

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6
Q

What type of tissue do x-rays normally target?

A

Bone.

-leukaemia

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7
Q

What type of tissue does oestrogen normally target?

A

Breast.

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8
Q

What organ does Hep B target (HBV)?

A

Liver.

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9
Q

What is a carcinogen?

A

Any agent that significantly increases the risk of developing cancer.

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10
Q

Carcinogens are often genotoxic. What does this mean?

A

Can chemically damage DNA and cause mutations.

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11
Q

What sort of carcinogens are genotoxic?

A

Initiators.

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12
Q

What is the effect of non-genotoxic carcinogens?

A

Induce proliferation and DNA replication.

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13
Q

What sort of carcinogens are non-genotoxic?

A

Promoters.

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14
Q

What are ‘complete’ carcinogens?

A

Both initiators and promoters.

-e.g. UV light

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15
Q

What does initiation require? (2)

A
  • Chemical modification of DNA

- Replication of modified DNA and mis-incorporation by DNA polymerase

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16
Q

What does initiation lead to?

A

An inherited mutation.

-if replicated twice

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17
Q

How do promoters contribute to carcinogenesis? (2)

A
  • Stimulate 2 rounds of DNA REPLICATION for mutation fixation
  • Stimulate CLONAL EXPANSION of mutated cells
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18
Q

Describe the general processes of initiation, promotion and progression.

A
  • Initiating agent damage DNA
  • Promoting agent fixes damage as mutation, and converts normal cell to mutant
  • Promoting agent stimulates clonal expansion&raquo_space; papillomas
  • Further clonal expansion; papilloma&raquo_space; carcinoma
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19
Q

What is the smallest change in DNA sequence that can cause a change in gene function?

A

Point mutation.

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20
Q

What is a Philadelphia chromosome?

A 
Translocation chr(9,22).
-associated with chronic myeloid leukaemia
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21
Q

What is the most common type of genetic abnormality in cancer genes?

A

Translocation.

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22
Q

What aneuploidy?

A

Abnormal number of chromosomes in a cell.

-e.g. 45 or 47

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23
Q

What proportion of our genes have CpG islands associated with promoter sequences?

A

~70%.

-cytosine followed by guanine

24
Q

What is the function of CpG islands?

A

Help to control gene expression.

-methylation only effective if within the promoter sequence

25
Q

What does abnormal methylation of gene promoters in TSGs lead to?

A

Epigenetic inactivation of tumour suppressor genes.

-most common inactivation

26
Q

What is the effect of mutations in oncogenes?

A

Gain of function.

27
Q

What mutations lead to loss of function in oncogenes but not tumour suppressor genes? (3)

A
  • Amplification
  • Translocations
  • Inversions
28
Q

What is the effect of mutations in tumour suppressor genes?

A

Loss of function.

29
Q

What mutations lead to loss of function in tumour suppressor genes but not oncogenes? (5)

A
  • Frameshifts
  • Insertions / deletions
  • Chromosomal rearrangements
  • Promoter methylation
  • Chromosome loss
30
Q

What dud Charlotte Auerbach show?

A

That chemicals can induce heritable genetic changes in organisms.
-induced eye colour change in flies

31
Q

What do the majority of carcinogens require to introduce a genetic influence?

A

Require metabolic activation by enzymes.

32
Q

Carcinogens; what does direct acting mean?

A

Interact directly with DNA.

-e.g. UV light, O2 radicals

33
Q

What is a procarcinogen?

A

A chemical that requires enzymatic activation before becoming carcinogenic.
-e.g. aromatic amines

34
Q

How is benzopyrene generated?

A

Combustion of organic material.

35
Q

What type of carcinogen is benzopyrene?

A

A pro-carcinogen.

-requires metabolic activation&raquo_space; BPDE to become carcinogenic

36
Q

What is xeroderma pigmentosum?

A

Autosomal recessive disorder.

  • defect in NER repair pathway
  • UV sensitivity, abnormal pigment, etc
37
Q

What do inherited defect in the ATM gene cause?

A 
Ataxia telangiectasia (A-T).
-  ^ cancer risk
38
Q

What is another name for Lynch syndrome?

A

Hereditary Non-Polposis Colorectal Cancer (HNPCC).

39
Q

What do mutations in repair processes lead to?

A

Increased disease.

40
Q

What are the main effects of carcinogenic exposure?

A
  • Metabolic activation

- DNA damage

41
Q

Genetic polymorphisms of which stages of carcinogen exposure affect susceptibility? (3)

A
  • Metabolic activation
  • DNA repair
  • Detoxification excretion
42
Q

How many carcinogens have been identified in tobacco smoke?

A

19.

-e.g. acrolein (acrid smell)

43
Q

What increases the risk of tobacco smoke leading to cancer?

A

Alcohol.

-100x increased risk of head / neck cancer

44
Q

What is alcohol converted to that can cause damage?

A

Acetaldehyde.

-damages DNA

45
Q

What are the main harmful effects of alcohol?

A
  • Increased oestrogen and testosterone
  • Increased uptake of chemicals into cells within upper GI
  • Reduced folate
  • Kills surface epithelium&raquo_space; proliferation
46
Q

What is folate needed for?

A

Accurate DNA replication and repair.

47
Q

What is the effect of oestrogen on breast cancer risk?

A

Increased oestrogen increases the risk of breast cancer.

48
Q

How does oestrogen increase the risk of breast cancer? (2)

A
  • Stimulates cell division

- Induces DNA damage

49
Q

What effect does delayed menarche (1st period) have on breast cancer risk?

A

Delayed menarche decreases breast cancer risk by 20% each year.

50
Q

What is oopherectomy?

A

Removal of the ovaries.

51
Q

What effect does oophrectomy have on the risk of breast cancer?

A

Oopherectomy decreases breast cancer risk by 90%.

52
Q

What is orchidectomy?

A

Removal of the testicles.

53
Q

What effect does orchidectomy have on the risk of prostate cancer?

A

Orchidectomy reduces the incidence of prostate cancer.

54
Q

What is the effect of chronic inflammation on cancer?

A

Chronic inflammation increases the risk of many types of cancer.
-e.g. colitis, hepatitis

55
Q

What is one the main cells in the link between inflammation and cancer?

A

Tumour-associated macrophages (TAMs).

-recruited by cytokines released from tumour cells

56
Q

What are the 2 main stages in the inflammatory response?

A

INITIATION - DNA damage from release of free radicals

PROMOTION - growth factor induced cell division

57
Q

What are the main categories of environmental factors that contribute to cancer?

A
  • Diet
  • Tobacco
  • Infection

Year 2 EMS MoD (20 decks)

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