Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2 MECHANISMS OF DISEASE > Carcinogenesis - Causes of Cancer > Flashcards

Carcinogenesis - Causes of Cancer Flashcards

1
Q

In what 5 ways are human carcinogens identified?

A
  1. studies in migrant populations represent geographical variations in risk
  2. occupational exposure
  3. accidental exposure
  4. big epidemiological surveys
  5. laboratory experiments involving rodents, human cells or bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does cancer incidence vary across the globe?

How does this affect migrants?

A

the incidence of cancer varies massively from one part of the world to another

this suggests that the environment plays a significant role in rates of cancer occurrence

migrants gradually adopt the pattern of cancer incidence of the country to which they emigrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why is occupation related to cancer risk?

A

Depending on occupation, workers may be exposed to specific types of carcinogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the carcinogen that workers involved in iron and steel industries are exposed to?

A

heavy metals such as cadmium and nickel

workers in aluminium production, coal gasification, coke production and iron and steel industries are affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What carcinogen are workers involved in mining of hematite and uranium exposed to?

A

radon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What cancer is common in workers involved in painting and making furniture?

A

they are exposed to various solvents and preservatives

many cases of cancer of the sinonasal cavities and paranasal sinuses have been reported among woodworkers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What carcinogen are workers in the rubber and dye industry exposed to?

A

ß-napthylamine and 4-aminobiphenyl

working in these industries is associated with bladder cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What type of cancer is often seen in patients employed in the boot and shoe manufacture and repair industry?

A

nasal adenocarcinoma

particularly when there is exposure to leather dust

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How are carcinogens classified and identified?

A

by IARC monographs

the potentially carcinogenic agents are put into groups depending on their cancer risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 5 categories of human carcinogens with examples?

A

chemicals:

  • PAHs
  • nitrosamines

Infectious agents:

  • human papilloma virus
  • Helicobacter pylori

radiation:

  • UV light
  • radon

minerals:

  • asbestos
  • heavy metals

physiological:

  • obesity
  • oestrogens and androgens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do all the human carcinogens have in common?

A

prolonged exposure to each agent (or a combination) can lead to the accumulation of genetic alterations in clonal populations of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does PAH stand for?

A

polycyclic aromatic hydrocarbons

these are a class of chemical agents that are produced whenever organic material is burnt

e.g. toast, meat, fossil fuels, tobacco

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are nitrosamines?

A

a class of chemical agent that are produced in the diet when amino acids have nitrogen groups attached to them

nitrites added as a preservative to processed foods are able to nitrosate amino acids and convert them into carcinogenic agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the target tissues for the following carcinogens?

A

HPV = human papilloma virus

HCV = hepatitis C virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the definition of a carcinogen?

What are the 2 types?

A

an agent that significantly increases the risk of developing cancer

they can be initiators or promoters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the difference between an initiator and a promoter?

A

initiator:

  • genotoxic
  • chemically modifies or damages DNA

promoter:

  • non-genotoxic
  • induces proliferation and DNA replication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is meant by a “complete carcinogen”?

A

they act as both an initiator and a promoter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the similarities and differences in the way oestrogen and reactive oxygen species (free radicals) act as carcinogens?

A

they are both promoters (non-genotoxic)

oestrogen induces proliferation as part of its normal physiological function

ROS are cytotoxic and lead to proliferation through the replacement of dead or damaged cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What 2 things are required for mutation induction (initiation) to go ahead?

A
  1. chemical modification of DNA
  2. replication of modified DNA and mis-incorporation by DNA polymerase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What errors usually occur during DNA replication?

What do these errors result in?

A

DNA polymerases make mistakes at a very low but significant rate

this results in the accumulation of genetic variation or polymorphisms in coding and non-coding sequences in the genome

some of these changes are deleterious and known as mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How can the presence of chemical modifications (miscoding or non-coding adducts or lesions) in DNA have negative effects?

A

the presence of chemical modifications exacerbates the tendency of polymerases to make mistakes (point mutations) by misincorporation

or it can cause the polymerase to leave a break in the DNA strand that can end up as a double-stranded DNA break

this is a substrate for deletions, insertions or translocations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What causes chemical modification of the nucleotides involved in base-pairing?

A
  1. environmental factors
  2. through the action of endogenous reactive molecules
    e. g. free radicals produced by normal physiological processes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In what way do agents that are good promoters contribute to carcinogenesis?

A
  1. they can stimulate the 2 rounds of DNA replication required for mutation fixation
  2. they can stimulate clonal expansion of mutated cells, which allows for accumulation of further mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

In the following model, what happens during initiation?

A
  1. genotoxic initiating agent damages DNA
  2. promoting agent fixes damage as a mutation and converts the normal cell into a mutant cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In the following model, what happens during promotion and progression?

A
  1. promotion stimulates clonal expansion of initated cell to produce papillomas
  2. further rounds of mutation and clonal expansion allows progression of papilloma to carcinoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is meant by an agent being “good” at initiating cancer?

A

the agent is good at inducing mutations

when these mutations occur in certain genes (e.g. RAS) they make the cell more susceptible to promotion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is meant by a promoter agent being cytotoxic?

A

it results in cell death, inflammation and stimulation of cell division in surviving cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why is cell division in response to a cytotoxic agent vitally important in mutation generation?

A

DNA replication in the presence of DNA damage is an error-prone process that can result in permanent changes in DNA sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What would repeated treatments with promoting agents lead to?

A

the gradual accumulation of mutations as a result of exposure to exogenous mutagens and endogenous mutagens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the relationship between cancer risk and cell turnover?

A

cancer risk is directly related to the levels of cell division

in cells with a higher turnover (e.g. in the bowel), there is a higher rate of DNA replication and more chance of developing cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the smallest change in DNA sequence that can give rise to a change in gene function?

A

a point mutation

this involves a change in a single nucleotide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the 2 types of point mutations?

A

missense:

caused by an amino acid substitution

nonsense:

caused by introduction of a stop codon into the coding sequence

this results in a truncated protein product

33
Q

How can point mutations affect protein function?

A

they can make protein products more active - gain of function

or make protein products less active - loss of function

34
Q

What is a frameshift mutation?

How does this affect the protein product?

A

gain or loss of one to several base pairs that results in a shift in the reading frame of a gene transcript

this changes the amino acid sequence downstream of the frameshift

this usually inactivates the protein product

35
Q

What types of mutation usually lead to a loss of function?

A

deletions or insertions of DNA fragments from or into a gene

this disrupts the amino acid sequence and leads to a loss of protein function

36
Q

What type of mutation usually leads to a gain of function for the cell?

A

gene amplification

this can result in a cell having anything up to a hundred copies of a gene, which it would normally only have 2 copies of

this leads to excessive amounts of protein and a gain of function

37
Q

What is meant by Philadelphia chromosome?

A

a translocation between chromosome 9 and 22

(a part of 22 breaks off and attaches to 9)

this causes chronic myeloid leukaemia

38
Q

How can chromosomal translocations affect genes?

A
  1. genes may be moved to a more transcriptionally active region of the chromosome
  2. genes may be recombined into new gene fusions
39
Q

What is meant by aneuploidy?

A

any departure from the normal structure or number of chromosomes

40
Q

Which types of mutations tend to lead to a gain of function?

What type of gene is implicated in gain of function in cancer?

A

proto-oncogenes are activated

this can occur by base pair substitutions, amplification, translocations or inversions

41
Q
A
42
Q

What types of mutations lead to a loss of function?

Which genes are implicated in cancer?

A

inactivation of tumour suppresor genes

this can occur by base pair substiturions, frameshifts, deletions, insertions, chromosomal rearrangements, chromosome loss or promoter methylation

43
Q

What is the difference between an oncogene and a proto-oncogene?

A

when a gain of function mutation in a gene confers a particular tumour characteristic to a cell, the mutant gene is an oncogene

the non-mutated version of the gene is the proto-oncogene

44
Q

What is meant by a “CpG island”?

What happens when it is methylated?

A

70% of genes have CpG islands associated with their promoter sequences

CpG methylation shuts down the expression of a gene if it occurs within the promoter sequence of a gene

45
Q

What is the most common way in which tumour suppressor genes are inactivated?

A

methylation of CpG islands within the promoter region of the gene

46
Q

What is the difference between a direct acting carcinogen and a procarcinogen?

A

direct acting:

  • interacts directly with DNA
  • e.g. oxygen radicals, nitrosamines, radiation

procarcinogens:

  • require enzymatic (metabolic) activation before they react with DNA
  • e.g. aromatic amines, PAHs
47
Q

What do the majority of carcinogens that we ingest require?

How is this affected by genetics?

A

the majority of carcinogens we ingest require metabolic activation by enzymes that normally function in the detoxification and excretion of toxic chemicals

there is a genetic influence on the extent to which we are sensitive to a genotoxic attack by different agents

48
Q

What would make someone more likely to get cancer after ingesting a carcinogen, relating to their genetics?

A

if someone activated a particular chemical more efficiently

or

they excrete an activated chemical less efficiently

49
Q

How is benzopyrene generated?

How does it act as a carcinogen?

A

it is generated through the combustion of most organic material, such as meat, tobacco and fuel

it is a procarcinogen that requires metabolic activation before it can react with DNA

50
Q

How has benzopyrene been used in laboratory experiments?

A

hotspots of DNA damage formed by the reaction of BPDE with the TP53 gene match the hotspots of mutation seen in this gene in the lung tumours of smokers

51
Q

What effects do different genotoxic agents (mutagens) have on DNA?

A

different mutagens can modify DNA in different ways

this results in lots of different mutational outcomes ranging in size and severity

52
Q

What helps to maintain the integrity of the genome?

A

various DNA repair processes

mutational defects in several of these processes can lead to cancer predisposition

53
Q

What can inherited defects in the NER repair pathway lead to?

A

xeroderma pigmentosum (XP)

this is a group of rare autosomal-recessive inherited disorders characterised by extreme skin sensitivity to UV light, abnormal skin pigmentation and high frequency of skin cancers

54
Q

What is the effect of inherited defects in the ATM gene involved in recombinational repair pathways?

A

ataxia telangiectasia (AT)

this is an aurosomal recessive disorder in which patients have an elevated incidence of cancers

this is 100-fold compared to normal

55
Q

How do AT cells react to X-rays?

A

AT cells have abnormal sensitivity to X-rays and radiomimetic chemicals

this leads to chromosome and chromatid breaks

56
Q
A
57
Q

W

A
58
Q
A
59
Q

How does the ATM gene product interact with other genes?

A

it interacts with the products of tumour suppressor genes, such as TP53 and BRCA1

AT families have reported an increased risk of breast cancer in women with one mutated ATM gene

60
Q

What mutation is responsible for hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome?

A

it is an autosomal dominant condition caused by mutations in one of several mismatch repair genes

the most common are MSH2 and MLH1

61
Q

What are patients with HNPCC at increased risk of?

A

an increased lifetime risk of developing colorectal cancer (amongst others)

62
Q

Why may groups of people suffering the same levels of exposure display a wide range of responses?

A

genetic polymorphisms in genes encoding metabolic activation, detoxification or DNA repair enzymes may confer greater or lesser susceptibility to the effects of carcinogenic exposure

63
Q

What are the 5 main levels of defence against carcinogens?

A
  1. dietary antioxidants
  2. detoxification mechanisms
  3. DNA repair enzymes
  4. apoptotic response to unrepaired DNA damage
  5. immune response to infection and abnormal cells
64
Q

How is the immune response involved in protecting against cancer?

A

if an abnormal protein is expressed on the surface of a cell, this is recognised by T cells

an immune response is started against the abnormal protein

65
Q

How many carcinogens are present in tobacco smoke?

Which are the most relevant?

A

33 carcinogens

  1. polycyclic aromatic hydrocarbons e.g benzopyrene
  2. acrolein
  3. nitrosamines
  4. radioactive lead and polonium
  5. heavy metals - cadmium, chromium
66
Q

What happens to cancer risk when tobacco smoke is combined with alcohol?

A

alcohol acts as a promoter and leads to a 100-fold increase for head and neck cancer

67
Q

What cancers are associated with alcohol consumption?

A

at least 7 types of cancer:

  1. mouth
  2. oesophagus
  3. pharynx
  4. larynx
  5. breast
  6. bowel
  7. liver
68
Q
A
69
Q

In what ways can alcohol act as a carcinogen?

A
  1. it is converted to acetaldehyde, which causes 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, needed for accurate DNA replication
  5. can kill surface epithelium and lead to unscheduled proliferation
70
Q

What are all the strongest risk factors for breast cancer related to?

A

they are all associated with increased exposure to oestrogen

this can both stimulate cell division and induce DNA damage

71
Q

What reduces risk of breast cancer?

A

breast cancer risk reduces 20% for each year the menarche is delayed

oopherectomy leads to 90% decrease in breast cancer

(orchiectomy reduces incidence of prostate cancer)

72
Q

What types of cancer are associated with chronic inflammation?

A
  1. colitis
  2. hepatitis
  3. Barrett’s metaplasia
  4. gastritis
  5. gallstones
73
Q

How does the inflammatory response act as both an initiator and a promoter?

A

initiation:

DNA damage from released free radicals by immune cells

promotion:

growth factor induced cell division to repair tissue damage

74
Q

What is the key cell in the link between inflammation and cancer?

What is their role?

A

tumour-associated macrophages (TAMs)

they are recruited by cytokines released by tumour cells and produce tumour necrosis factor alpha (TNF-a)

TNF-a induces and maintains the inflammatory response

75
Q

In what other ways can TAMs lead to cancer?

A

they release reactive oxygen and nitrogen species that act as complete carcinogens

this results in mutation by damaging DNA and stimulating proliferation through induction of growth factors

76
Q

How can ROS secreted by TAMs and tumour cells affect fibroblasts?

A

they induce fibroblasts to undergo autophagy

this releases important nutrients that tumour cells can “feed” on

77
Q

How can diet affect risk of cancer?

A

exposure to carcinogens in red meat, burnt food and heavy metals can raise incidence

absence of protective factors such as fibre and antioxidants can also raise incidence

78
Q
A

Y2 MECHANISMS OF DISEASE (36 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions