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EMS - Mechanisms of Disease > 17. Causes of Cancer > Flashcards

17. Causes of Cancer Flashcards

1
Q

how are human carcinogens identified?

A
  1. geographical variance in risk
  2. occupational exposure
  3. accidental exposure
  4. big epidemiological surveys
  5. laboratory experiments
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2
Q

what are the categories of human carcinogens?

A 
chemicals
infectious agents
radiation
minerals
physiological
chronic inflammation
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3
Q

what tissues does alcohol affect?

A

pharynx, larynx, oesophagus, liver

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4
Q

what tissues does asbestos affect?

A

lung, pleura

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5
Q

which carcinogen affects the bone marrow?

A

x rays

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6
Q

which carcinogen affects the skin?

A

UV light

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7
Q

which carcinogen affects breast tissue?

A

Oestrogen

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8
Q

which tissues does tobacco smoke affect?

A

mouth, lung, oesophagus, pancreas, kidney, bladder, etc.

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9
Q

which carcinogens affect the liver?

A

Aflatoxin and Hep B

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10
Q

which carcinogen affects the cervix?

A

HPV

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11
Q

what is a carcinogen?

A

any agent that significantly increases the risk of developing cancer

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12
Q

what are the 3 functional types of carcinogens?

A
  1. initiators
  2. promoters
  3. complete
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13
Q

how do initiators work?

A

can chemically modify or damage DNA (genotoxic). 2 steps -

  1. chemical modification of DNA
  2. replication of modified DNA and mis-incorporation by DNA polymerase
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14
Q

how do promoters work?

A

non genotoxic
induce proliferation and DNA replications either
a. stimulate 2 rounds of DNA replication required for mutation fixation
b. stimulate clonal expansion of mutated cells, enabling accumulation of further mutations

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15
Q

how do complete carcinogens work?

A

they can both initiate and promote

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16
Q

how does tissue progress from a mutation to cancer?

A
  1. genotoxic initiating agent damages DNA
  2. promoting agent fixes damage as a mutation and converts normal cell into mutant initiated cell
  3. promoting agent stimulates clonal expansion of initiated cell to produce papillomas
  4. further rounds of mutation and clonal expansion allows the papilloma to progress into a carcinoma
17
Q

what are the common genetic abnormalities seen in cancers/

A 
base pair substitutions
frameshift
deletion
gene amplification
chromosomal translocation
chromosomal inversion
aneuploidy
18
Q

which is the most common way of inactivating tumour suppressor genes?

A

methylation

19
Q

what are the functional consequences of mutation?

A

mutations in oncogenes lead to a gain of function

mutations in TSGs lead to a loss of function

20
Q

how are carcinogens classified according to metabolic activation?

A
  1. direct acting - interact directly with DNA

2. pro carcinogens - require enzymatic activation before they react with DNA

21
Q

what are the steps in the metabolic activation of benzopyrene?

A
  1. benzopyrene
  2. benzopyrene 7,8-epoxide
  3. benzopyrene 7,8- dihydrodiol
  4. benzopyrene 7,8-diol, 9-10-epoxide (BPDE)
22
Q

which process are in place to repair damaged DNA?

A

base excision repair
nucleotide excision repair
recombinational repair
mismatch repair

23
Q

what protective mechanisms does the body have in place to prevent cancer?

A
  1. prevention of metabolic activation of the carcinogen
  2. dietary antioxidants
  3. detoxification mechanisms
  4. DNA repair enzymes
  5. apoptotic response to unprepared genetic damage
  6. immune response to infection and abnormal cells
24
Q

how many carcinogens does tobacco smoke have?

A

19

25
Q

why is alcohol considered a carcinogen?

A
  1. converted to acetaldehyde in the liver, can cause DNA damage
  2. increases levels of oestrogen and testosterone
  3. increases uptake of carcinogenic chemicals into cells within the upper GI tract
  4. reduces levels of folate
  5. kills surface epithelium, leading to unscheduled proliferation
26
Q

why is oestrogen considered a carcinogen?

A

it can both stimulate cell division and induce DNA damage

27
Q

how does chronic inflammation play a role in cancer?

A
  1. DNA damage from release of free radicals by immune cells - initiation
  2. growth factor induced cell division to repair tissue damage - promotion
28
Q

examples of inflammatory diseases associated with cancer

A 
colitis
hepatitis
barrett's metaplasia
gastritis
gallstones

EMS - Mechanisms of Disease (16 decks)

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