Neoplasia 3 Flashcards
(56 cards)
1
Q
Carcinogenesis=
A
causes of cancer
2
Q
name some intrinsic factors of neplasia
A
Hereditary
- Autosomal dominant genes most likely to cause tumour in the young
- Will develop neoplasia
- E.g. breast cancer
- Less frequent genes- neoplastic phenotype
- Multiple abnormalities which lead to an increased risk
Age
- The older you are the longer you’ve had to develop
Sex (particularly hormone)
- E.g. breast cancer predominately a female cancer due to oestrogen exposure
3
Q
Extrinsic factors
A
Environment
- Chemical
- Radiation
- X-ray
Infection
- HPV
Behaviour (30%)
- Tobacco smoke
- Obesity
- Sun exposure (UV damage)
- Alcohol
- Lack of exercise (independent to BMI)
4
Q
Being overweight and obese is the 2nd biggest cause of cancer
A
Keeping a healthy weight reduces the risk of 13 different types of cancer
5
Q
smoking is the biggest
A
preventable cause of cancer (25%)
6
Q
which cancers is smoking a risk factor for?
A
- Lung cancer 7/10- most common cause of cancer death
- Mouth
- Pharynx
- Nose
- And sinuses
- Larynx
- Oesophagus
- Liver
- Pancreas
- Stomach
- Kidney
- Bowel
- Ovary
- Bladder
- Cervix
- Some type of leukaemia
7
Q
if you drink and smoke it increases your risk of which cancers
A
upper airwars and digestive tract cancer
8
Q
evidence of cancer
A
- Animal studies
- Epidemiological studies
- Studies of migrating population
- Look at baseline risk in original country
- Then look at the rate of cancer once they have migrated
- E,g, Japanese migrants to USA
9
Q
approx how much of cancer risk is due to environment/ extrinsic factors
A
85%
10
Q
example of a chemical that is a carcinogen
A
2-napthylamine (also present in smoke) is an industrial carcinogen used in the dye manufacturing industry
11
Q
2-napthylamine
A
This dye causes cancer
12
Q
Malignant neoplasms caused by 2-napthylamine showed that:
A
- There is a long delay between carcinogen exposure and malignant neoplasm onset
- The risk of cancer depends on total carcinogen dosage
- There is sometimes organ specificity for particular carcinogens e.g. bladder cancer
13
Q
A
14
Q
chemical carcinogenesis involves
A
initiation and promotion
15
Q
initiation and promotion
A
- Sequence in which carcinogens are administered is critical
- Initiators must be given first
- Followed by a second class carcinogen called promoters
16
Q
Test used to tell if chemical is a carcinogen
A
AIMS test
17
Q
AIMs test
A
positive result- carcinogen capable of causing mutation
18
Q
why is rat liver used in AIMs test?
A
most chemicals are pro-carcinogens until they are been activated in the liver (by cytochrome P450)
19
Q
people with germline mutations get
A
cancer earlier
- neoplastic cells get a head start
20
Q
an initiator=
A
anything that causes mutation e.g. radiation
21
Q
promoters
A
anything that causes expansion of that population
22
Q
examples of chemicals
A
- polycyclic aromatic hydrocarbons
- aromatic amines
- N-nitroso compounds
- alkylating agents
- natural products
23
Q
example of aklylating agent
A
Vinyl chloride
- mainly found in factories
24
Q
natural products
A
aflatoxin B1
- found in virus- liver cancer
25
asbestos
natural products
- okay if left as it is
- as soon as disrupted will be inhalte and irritate alveoli
- both initiator and promotor
26
type of radiation that are mutagenic
Alpha
Beta
Gamma
X ray
Uv ray
27
how can radiation cause cancer
* damage DNA directly
* or indirectly generating free radicals
28
how does radiation create free radicals
by crashing into water
29
25% of all malignant neoplasms are
skin neoplasms- UV
30
sources of ionising radiation
- radon gas
- medical tests
31
infections and cancer
* Some infections **directly** affect genes that control cell growth
* Others do so **indirectly** by causing chronic tissue injury and the resulting regeneration acts either as a promoter for pre-existing mutations or causes new mutations from DNA replication errors
32
example of infection with direct effect
HPV
33
Indirect effect
HEP B virus
- chronic inflammation= promotor
34
Human papilloma virus (HPV)
* Makes 2 proteins E6 and E7
* Virus infects cell
* ensures it doesn’t die and then hijacks its DNA replication machinery to make more virus particles
* E6 inhibits P53 which prevents cells from undergoing apoptosis
* Hijacks cell cycle by interfering with Rb protein which is an important cell cycle checkpoint
35
example of an inherited cancer
retinoblastoma - rare tumour of the eye
36
how many Rb cases are familial or sporadic
40% familial
60% sporadically
37
familial Rb
* Autosomal dominant means more likely to get it young
* Occurs early
* Can affect both eyes
38
Sporadic Rb
* In one eye
* Generally, aren’t at increased risk of other cancer
* Need 2 sporadic hits (mutations)
* Occurs later
39
Tumour suppressors
* Normal function to stop proliferation
* Loss of function
* Most instances both alleles must be damaged for transformation to occur
* Abnormalities in these genes leads to failure of growth inhibition
40
example of tumour suppressor gene
Retinoblastoma gene
* Key gene regulation of G1/s cell cycle checkpoint
* Also controls cellular differentiation
41
Proto-oncogenes
* Drive proliferation
* Gain of function mutation
42
example of protooncogene
* Most common type of abnormalities involving proto-oncogenes in human tumours
* They are mutated in approx. 15-20% of all malignant neoplasm
* Some types of cancers the frequency of RAS mutation is much higher e.g. 90% of pancreatic adenocarcinomas
* They were discovered initially in transforming retroviruses (HIV)
43
protoncogenes and tumour suppressor genes
play opposing roles in the cell signalling pathways
44
accumulation of mutations leads to
malignant cancers
45
proto-oncogenes can encode
* growth factors (e.g. PGDF),
* growth factor receptors ( e.g. HER2),
* plasma membrane signal transducers (e.g. RAS),
* intracellular kinases (e.g. BRAF),
* transcription factors (e.g. MYC),
* cell cycle regulators (e.g. Cyclin D1) apoptosis regulators (e.g. BCL2)
46
DNA repair genes
* caretakers genes prevent accumulation of DNA damage
* familial cancer syndromes help our understaning
* some inherited cancer syndromes have germline mutations that indirectly affect DNA repair
47
familial breast cancer
* BRAC1/ BRAC2 genes
* Involved in repairing double strand DNA breaks
* Can also be found in sporadic malignant neoplasms
48
Chromosome aggregation during mitosis can also be abnormal in malignant cells
* Alterations account for accelerated mutations found in malignant neoplasms known as genetic instability
* Genes that maintain stability belong to a class of tumour suppressor genes called caretaker genes
49
malignant neoplasm = ................... mutations
10 or less
50
hallmarks of cancer (6)
1. Self sufficiency in growth signals
2. Resistance to growth stop signals – TSG’s (tumour suppressor genes)
3. Cell immortalisation (no limitation on the number of times a cell can divide)
4. Sustained ability to induce new blood vessels (angiogenesis)
5. Resistance to apoptosis
6. Ability to invade and produce metastases
51
example of self0sufficient growth signal
HER2 gene amplification (breast cancer)
52
example of resistance to anti-growth signals
CDKN2A gene deltion
(CDK inhibitor)
Melanoma
53
example of grow indefinitley
telomorase gene activation
- most cancers
54
example of induce new blood vessels
activation of VEGF expression
- many cancers
55
example of resistance to apoptosis
BCL2 gene translocation (lymphoma)
56
example of inavade and produce metastases
E-cadherin mutation
- gastric cancer
