Flashcards in How and why neoplasms occur Deck (45)
What are the 5 leading extrinsic risk factors for neoplasms?
- high BMI
- low fruit and veg
- lack of exercise
- tobbaco use
- alcohol use
What are the intrinsic risk factors for neoplasms?
What are the 3 categories of extrinsic risk factors for neoplasms?
does intrinic or extrinsic factors have a bigger effect on cancer risk?
Which chemical is well known to be linked with bladder carinoma?
2- napthylamine from dye manufacturing
What 4 principles about chemical carcinogens does 2- napthylamine illustrate?
- long delay between exposure and malignant neoplasm onset
- risk of cancer depends on total carcinogen dose
- sometimes organ specificity for specific carcinogens
- chemical carcinogenesis involves initiation and promotion
state some industrial carcinogens which have an effect on relevant workers?
- coal tars
- vinyl chloride
What malignancies does asbestos lead to?
What is the two hit hypothesis?
That both tumour suppressor gene alleles are needed to be mutated in order to cause a neoplasm
What is the significance of the two hit hypothesis with regard to familial cancers?
in familial cancers the first hit is delivered from the germ line so all cells have one allele of the tumour suppressor gene which is faulty. this means they only need one more mutation for initiation of the neoplasm
Name some chemical carcinogens
polycyclic aromatic hydrocarbons, aromatic amines, N- nitroso compounds, alkylating agents
name and describe the test which shows that initiators are muatgens while promotors cause proliferation
- ames test
- salmonella which requires histidine and rat liver extract in tubes
- to one tube add mutagens and then culture on agar without histidine
- on other dont add mutagens
- on mutagen and no histidine salmonella agar lots grow as mutate to not need histidine
- on agar with no mutagens few or no colonies grow as lower rate of mutations
What is a procarcinogen and a complete carcinogen?
a procarcinogen is only carcinogenic when metabolised by CYP450 in liver
a complete carcinogen is both an initiator and a promotor
What radiation can cause mutations?
UV light (skin only)
a, b and y rays
How can radiation damage DNA?
- direct damage (alters bases, single/ ds breaks)
- indirect damage (create free radials)
By what general mechanisms can infections be carcinogenic?
- directly: mutate/ affect genes which control cell growth
- indirectly: cause chronic injury, regeneration causes new DNA mutations due to arise due to replication errors and also act as promotors for preexisting mutations
How does HPV lead to increased risk of cervical cancer?
it expresses E6 +E7 - E6 inhibits P53 which interferes with retinoblastoma protein- both of which are tumour supressor genes - prevents apoptosis. Basically hijacks the cell cycle
How do hep B and C lead to increased risk of hepatocellular carcinoma?
cause liver cirrhois
lead to chronic inflammation and regeneration which increases risk of mutation and is also a promotor
How does HIV lead to cancer and what type?
lowers immunity so more suseptible to human herpres virus 8 which leads to kasopsis sarcoma
How many protoonco alleles need to be mutated to cause initiation?
How does RAS mutation lead to cancer?
- RAS is G protein (proto-oncogene) which is needed to activate cyclin D and so cause cell cycle to pass restriction point
- RAS becomes mutated so GTP always binds to it so its always active
- cell now looses control of when it is allowed to divide
RAS is therefor a protooncogene
How does mutation of retinoblastoma protein lead to cancer?
it inhibits passage through the restriction point.
therefore when it is mutated its not expressed and so cell can go through cell cycle without inhibition.
RB is therefore a tumour supressor gene
give examples of other things that can be coded for by proto- oncogenes and the 2 important examples we need to know
- growth factor receptors (HER2)
- transcription factors (c- MYC)
- signal transducers (RAS)
- growth factors
- cell regulators (eg Cyclin)
- apoptosis regulators (BCL2)
Other than retinoblastoma protein, what is the other tumour surpressor gene we need to know about?
What is a caretaker gene?
genes that maintain the genetic stability of a cell- they're a type of tumour supressor gene that prevent accumulation of DNA damage.
What familial caretaker gene mutation generally leads to xeroderma pigmentosum (auto ressesive condition which causes many skin cancers at a young age) and how does this occur?
- mutation of one of the nucleotide excision repair genes
- cells more suseptible to UV damage
- more melanoma
What is the inheritance pattern of hereditary non- polyposis colon cancer (HNPCC) and what genes are mutated?
- genes that help with mismatch repair
- leads to microsatallite instability
- autosomal dominant
What genes are mutated in familial (but also sporadic) breast carinoma, how does this affect genetic stability?
- BRAC1 and 2
- they repair double strand breaks
- leads to chromosomal instability
- damaged DNA not repaired, massively increases risk of cancer
What are the 6 hall marks of cancer
1) self sufficiency in growth signals (oncogenes)
2)resistance to growth stopping signals (TSG's)
3) no limit on number of times a cell can divide (cell immortalisation)
4) sustained ability for angiogenesis
5) resistance to apoptosis
6) ability to invade and produce metastases
genetic instability is an enabling characteristic