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PHT801 UNIT 1 & 2 > Unit 2: history of cancer and environment > Flashcards

Unit 2: history of cancer and environment Flashcards

1
Q

When were bone tumours found in the first vertebrates?

A

Bone tumours were found 350 million years ago in fossil fish

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2
Q

What cancer was found in fossils 75 million years ago and in what kind of fossils were they found in?

A

Bone cancer (osteocarcinoma) were found in diasour fossils 75 million years ago.

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3
Q

When was the earliest cancer case in a hominid?

A

1.7 million years ago a homonid foot bone tumour was found in south africa.

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4
Q

What cancers were found in ancient egypt 3000BC

A

Nasopharyngeal and bone cancers in mummies.

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5
Q

What type of cacner was found in Peru 400BC

A

metastatic melanoma was found in inca mummy skull bones.

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6
Q

What kind of cancer was found from skeletal evidence from medieval europe?

A

Osteosarcoma was found in skeletal evidence.

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7
Q

Was the insidence of cancer lower/higher in histroy compared to that of the modern day?

A

Incidence of cancer was lower. Only ~270 cases have been discovered throughout history

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8
Q

What factors need to be considered when suggesting a lower incidence of cancer histroically compared to that of modern day?

A 
Cancer incidence may appear to be lower due to...
- Environmental/lifestyle differences
- Smaller poppulation?
- lower life expectancy?
- poor tissue preservation as only bone 
  tumours are preserved in fossils?
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9
Q

What was the first written record of cancer?

A

Smyth papyrus 3000BC ancient egyptians - surgical manual telling how to visually diagnose and treat camcer

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10
Q

What was the demonic theory of cancer?

A

Cancer was caused by angry gods

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11
Q

What treatment methods were there for cancer during 3000BC

A
  • Prayers
  • spells
  • amulets
  • crude local surgery
  • cautery
  • herbal & arsnic pastes
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12
Q

What surgical factors were used in 3000BC

A

Alcohol for anaesthsia and honey for infection

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13
Q

What was the first clinical record of cancer?

A

1000-250BC CHINA

‘‘Nejing’’ - described clinical picture of breast cancer and its prognosis

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14
Q

What treatment methods were specialist physicians using to treat cancer as described in ‘‘nejing’’

A

Spiritual, herbal, diet and acupuncture

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15
Q

Why was the word carcinos used to describe cacner and who used this word?

A

Hippocrates described tumours to appear to be crab like with claws so used ‘‘karkinos’’ (translates to carcinoma)

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16
Q

What does the word oncos mean

A

Means mass hence oncos –> oncology

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17
Q

When was the latin translation to cancer first described?

A

50AD - Celcus provided the latin tranlation to cancer and visially described many tumours.

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18
Q

What were cancer treatments in ancient greece and rome

A
  • oils and pastes
  • purgatives
  • concoction of boiled ash
    of crabs with egg
  • powdered falcon faeces
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19
Q

how was cancer percieved in the ancient world?

A

Broadly seen as incurable throughout the ancient world

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20
Q

What was the first biologicaly based theory of cacner development?

A

4 humours (fluids)

  • pure blood = happy
  • black bile = depressed
  • yellow bile = angry
  • white bile = phlegmatic
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21
Q

What activities were seen to balance the 4 humours

A

Mensturation, breast feeding and ejaculation

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22
Q

Which physician supported hippocrates theroy of 4 humours?

A

Claudius Galen supported the humoral theory in 160AD and believed that excess black bile caused aggressiv, ulcerated cancer.

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23
Q

Waht cancer treatments were used by Galen

A

Wanted to eliminate black bile so blood letting, purgatives and herbal and sulpher mixtures were used.

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24
Q

How long did the Humoural theory underpin cancer treatment for?

A

1500 years after the humoural theory was established. It was believed through the islamic empire and christian europe, through the middle ages and into the 17th century.

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25
Q

Why was cancer largely seen as a female disease in history?

A

Because superficial cancers were seen in breast and skin while male internal cancers were left undiagnosed.

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26
Q

How was cancer percieved in modern history?

A

Cancer was still seen as incurable as it couldnt be managed effectively and so would progress.

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27
Q

Which anatomist undermined the humoural theory in the 16th century and how?

A

Andreas vesalius produced an atlas called the fabric of the human body where no black bile was found.

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28
Q

Who discovered blood circulation in the 17th century?

A

William harvey carried out autopsies and discovered how blood circulated around the body further disproving the humoural theory.

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29
Q

What physician carried out routine postmortem dissections?

A

Morgagni

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30
Q

What was the lymph theory for carcinogenesis

A

Cancer developes from decomposing lymph fluid as lymph was seen as abundant (unlike black bile) - by Stahl and Hoffman

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31
Q

How and when did surgery for cancer become much more routine?

A

By 18th century - Johannes scultetus performed ground breaking total mastectomy as anatomical research became more sophisticated.

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32
Q

What was the parasite theory

A

Breast cacner spread among hoouseholds and cancer treatment should take place outside of the city

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33
Q

Name 3 emerging links to cancer caused by environment and lifestye in the 19th centure

A 
- Scrotum cancer was 
  common among chimney 
  sweeps
- Nasal cacner and 
  tobacco
- High breast cancer but 
  no cervical cancer in 
  nuns as opposed to 
  married women
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34
Q

What was a landmark study of metastasis

A

Surgeon microscopist, Stephen Paget studdied autopsy of >700 breast cancer and realised that there was a preference of spread to the liver

35
Q

Who founded the seed and soil theory

A

Stephen Paget

36
Q

What is the seed and soil theory

A

Ability of the cancer (seed) disseminating via the circulatory system to form a metastatic deposit is DEPENDANT on whether the tissue has a hospitbale environment (the soil) which will allow the cancer to survive and proliferate.

37
Q

What locations are cancer incidence highest?

A

USA, Australia, Northern Europe

38
Q

Where are the lowest incidence of cancer

A

Japan and africa

39
Q

What location is breast cancer highest and lowest

A

High in USA

Low in Japan

40
Q

Where is stomach cancer highest and lowest

A

High in Japan

Low in USA

41
Q

Is there a link between geographical location and cancer risk related to a specific type?

A

Yes, environmental contribution is a key factor - diet, lifestyle, chemical environment

42
Q

Give an exampe of population data which shows an environmental link to cancer through geographical movement

A

People living in japan have high incidence of stomach cancer however when they migrate to hawaii =, levels of stomch cancer drop to the levels seen in hawaiian caucasians - shows as japanese people migrated to hawaii they aquired the lower risk rate of stomach cancer associated with the region, wheras incidence of breast cancer increases to that of hawaii.

43
Q

What report did Doll & Peto produce and what were its conclusions?

A

The causes of cancer - Most cancer is acredited to environmental factors with as much as 80% of cancer may be caused by environmental factors.

44
Q

What environmental and lifestyle factors are related to carcinogenesis

A

Diet - additives, preservatives, charred meat
Smoking - 1.2 million deaths
Alcohol - 1.4 million deaths
Reproductive life choices - early pregnancy, breastfeeding
Infectious contribution - HPV virus (viral oncoprotein interferes with tumour supressors)

45
Q

What is ionising radiation and how does it contribute to cancer. Name some examples of these radiations and what cancers can they cause?

A

Ionising radiation - atomic particles which can ionise (remove electrons) from the medium which they pass e.g X-rays, Gamma rays from cosmic radiation, beta/alpha radioactive particles, radiation from nuclear bombs.
causes leukemias and thyroid cancers

46
Q

What is non-ionising radiation? Name some examples

A

Any electromagnetic radiation which doesnt have eneough energy to ionise atoms or molecules, e.g - UV radiation

47
Q

Name 2 physical agents and 2 chemical agents which contribute to cancer

A

Physical - X-rays, UV rays
Chemical - industrial chemicals such as coal, cigarette
smoke –> releases polycyclic
hydrocarbons (PAHs) (chemicals with many
carbons and hydrogens)
Pestecides

48
Q

Name an ocupational risk factor associated with cancer

A

Asbestos causes mesothelioma (lining of lungs)

soot from chimney sweeping causes scrotum cancer

49
Q

What are the WHO cancer classifications

A 
Catagory 1 = carcinogenic to humans
Catagory 2a = probably carcinogenic
Catagory 2b = Possible carcinogenic
Catagory 3 = not classified to be carcinogenic 
Catagory 4 = probably not carcinogenic
50
Q

What is the % of cancer deaths attributed to diet and lifestyle in the USA

A

~85%

51
Q

What is the % of cancer deaths attributed to dphysical/chemical environment in the USA

A

~15%

52
Q

What is a gene mutatiion

A

Changes in DNA nucleotide sequence

53
Q

How to oncogenes and tumour supressors enable cancer

A

Mutations which activate oncogenes and/or cause loss of tumour supressors enable cancer initiation

54
Q

name some DNA repair mechanisms

A

DNA polymerase

Nucleotide excision repair

55
Q

What % of cancer is attributed to inherited germ line mutations and name an example

A

~10% such as BRACA1 mutation –> 5% of breast cancers

56
Q

What is an endogenous factor and give an example

A

Something which causes a SPONTANIOUS mutation e.g - errors in DNA proof reading during replication or
base loss during normal chemical reactions

57
Q

What does depurination cause

A

A or G loss from base pairs

58
Q

What does deamination cause

A

removing an amino group from a molecule = affects C, A, G bases.

59
Q

How can metabolism cause endogenous mutations

A

Reactive oxygen species can form due to normal cell metabolism which oxidises DNA bases and causes strand breaks resulting in a mutation.

60
Q

What is an exogenous factor

A

Aquired factors from diet/lifestyle/environment which causes INDUCED mutations

61
Q

What is a mutagen and give 2 examples

A

A physical/chemical agent which is a POTENT damager of DNA and therfore causes mutations
1. Ionising radiation alters DNA directly
2. Electrophilic chemicles which covalently modify
DNA (e- donor)

62
Q

What is an alkylating agent

A

An agent which alters DNA by adding an alkyl group (CH group) which drives DNA base loss or increases missreading errors

63
Q

What is an ultimate carcinogen

A

Chemicals which are ACTIVATED into very potent mutagens via metabolism in cells - which are able to covelantly bind to DNA bases forming adducts which distort the helix and cause misreading errors and mutations.

64
Q

What is a PAH and how is it produced and converted into an ultimate carcinogen

A

Polycyclic Aromatic Hydrocarbon - from burning fossil fuels can be converted by liver enzymes into an ultimate carcinogen

65
Q

What protein is known as the guardian of the genome

A

p53

66
Q

What causes damage to the gene coding for p53 by forming a DNA adduct

A

Benzopyrine causes a G-T substitution causing a mutation in the DNA which codes for p53

67
Q

What is a carcinogen

A

An agent which INITIATES and causes cancer - many carcinogens are also mutagens (permenantly damage DNA)

68
Q

List 3 tumour initiators

A
  1. PAH
  2. Ionising radiation
  3. alkylating agents
69
Q

What is a tumour promoter

A

Carcinogens which are mitogenic ONLY - dont produce mutations. only activate proliferation pathways.

70
Q

What is the Ames test for mutagens

A

Method which determines if a chemical is mutagenic or not.

71
Q

How does asbestos cause mesothelioma? And what effect does this have on the lungs?

A

Fibres are inhaled which enter cells and cause cancer. The tumours cause a plural effusion which builds up in chest cavity and compresses the lungs.

72
Q

What inherited mutation makes people more susceptible to asbestos induces mesothelioma

A

Mutations in the DNA repair gene BAP1

73
Q

Is asbestos a promoter or mediator of carcinogenesis

A

Both, asbestos can act directly or indirectly at all steps of carcinogenesis to promote MM

74
Q

What is the chromasome tangling theory for asbestos

A

Fibres act as a tumour INITIATOR and interfere with chromasome seperationduring mitosis causing DNA strand breaks and mutations

75
Q

What is the adsorbtion theory for asbestos

A

Fibres act as tumour INITIATOR by carrying carcinogens from cigarette smoke which causes DNA damage

76
Q

What is the oxidative stress theory

A

Macrophages produce ROS when trying and failing to engulf large asbestos fibres due to stress - ROS oxidises DNA causing mutauion.

77
Q

How can asbestos act as a tumour promoter

A

When inhaled, asbestos promotes chronic inflamation which activates proliferation signalling therefore acting as PROMOTERS in mesothelial cells which already have mutations.

78
Q

What 2 non-melanoma types of skin cancer are caused by UV radiation and in what cells do they develope?

A
  • develpes in keratinocytes
  • basal cell carcinoma (non-fatal)
  • Squamous cell carcinoma (fatal)
79
Q

What is a fatal skin cancer is caused by UV radiation and in what cells does it develop?

A

Melanoma - developes in skins melanocytes

80
Q

What two wavelengths of UV light are there and how carcinogenic are they?

A

UVA - longer wavelength which penetrates deeper
into the dermis, however has lower energy so
less carcinogenic.
UVB - Shorter wavelength which penetrates only into
the epidermis. However has a short
wavelength
and is highly carcinogenic.

81
Q

How does UVB cause carcinogenesis (and UVA to a lesser extent)

A

UBV energy is directly absorbed and breaks the double bond in the DNA pyrimidine ring (T,C). If this occurs next to another broken ring the DNA can form new covelant bonds producing a photoproduct = T-T or C-C dimmer. If this dimer isnt repaired it can cause mutation in p53 = leads to fatal non-melanoma skin cancer.

82
Q

What 2 types of photoproducts exist due to UVB and UVA radiation damage

A

64pp’s (pyrimidine 6-4 photoproduct) –> Formed by 1 new bond.

CPD’s (cyclobutane pyrimidine dimers) –> Formed by 2 new bonds, which distorts double helix so sequence is missread

83
Q

What is the signature mutation for UV damage

A

A bases are preferentially inserted in areas of dimers. Therfore when theres a C-C dimer it’s paired with an A. So when this is read it provides a T-T dimer = signature mutation.

84
Q

How does UVA cause carcinogenesis

A

It indirectly damages DNA by triggering ROS production in water molecules within melanocytes which oxidises DNA bases and causes mutation.

e.g - GUANINE + UVA —> 8-OXO-DEOXYGUANOSINE
error (8-oxo-dG)
8-oxo-dG misspairs with A instead of C = Mutation

PHT801 UNIT 1 & 2 (4 decks)

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