15 Neoplasia 3 Flashcards
Define Carcinogenesis.
causes of cancer
What are the INTRINSIC factors which account for cancer risk? (in general terms)
- Heredity
- Age
- Sex (hormonal)
What are the EXTRINSIC factors which account for cancer risk?(in general terms)
- Environment
- Behaviour
What are the 5 leading behavioural and dietary risks that account for 30% of cancer deaths?
- Smoking
- Alcohol
- Not enough fruit and veg
- Lack of physical activity
- High BMI
What % of cancer deaths deaths does tobacco smoke account for?
about 25%
What are the 3 main categories of EXTRINSIC carcinogens?
- Chemicals 2.Radiation 3. Infections
With relation to carcinogens, what factors affect the risk of cancer/cancer itself? (3)
1) Time between exposure and onset of malignancy
2) Total dosage
3) Organ (some carcinogens have organ specificity)
What two processes need to occur in sequence for chemical carcinogenesis to occur?
Initiation then promotion (some carcinogens= initiators, some =promoters)
What did the ‘Ames test’ show?
Initiators= mutagens
Promoters= cause prolonged proliferation in target tissues
–> all cause monoclonal expansion of mutant cells
How are chemical carcinogens classified?
- Polycyclic aromatic carcinogens
- Aromatic amines
- N-nitrosocompounds
- Alkylating agents
- Diverse natural products e.g. asbestos
What is a ‘complete carcinogen’?
Carcinogen which acts as initiator and promoter
What are pro-carcinogens?
chemicals- converted to carcinogens by P450 enzyme
How can radiation damage DNA?
DIRECTLY / INDIRECTLY- generates free radicals. Ionising radiation- damages DNA bases, causes single and double strand breaks
Apart from UV radiation, what is the other main source of radiation people are exposed to?
Natural background radiation from earth’s crust- radon
How are some infections directly carcinogenic?
Affect genes that control cell growth
How are some infections indirectly carcinogenic?
Cause chronic tissue injury- resulting regeneration
Give examples of infections which can be carcinogenic and how?
1) HPV- human papilloma virus-cervical carcinoma. Inhibits p53 and pRB function (DIRECT) 2) Hep B and C- chronic cell injury 3) Helicobacter pylori- chronic gastric inflammation 4)Parasitic flukes- inflammation in bile ducts 5)HIV- lowering immunity- allows potentially carcinogenic infections to occur
Give an example of an inherited predisposition to a malignancy.
Retinoblastoma- through germline mutations.
What is Knudson’s ‘Two hit hypothesis’?
=explains differences between familial tumour patterns and sporadic tumours (e.g. with retinoblastoma). FAMILIAL cancers- first mutation is in gremlin (all cells in body), second is somatic mutation SPORADIC cancers- requires 2 somatic mutations
What types of genes does Knudson’s ‘Two hit hypothesis’ refer to?
Tumour supressor genes (only require 1 oncogene to favour neoplastic growth (i.e. proto-oncogene mutation))
Give an example of an oncogene and how is causes neoplasm?
Mutant RAS encodes small G protein- pushes cell past restriction point. Mutant RAS= always active.
Give and example of a tumour suppressor gene.
RB gene
What is Xeroderma pigmentosum (XP)?
Autosomal recessive disease- mutation in DNA NUCLEOTIDE EXCISION REPAIR (NER) (caretaker gene)-patients= v sensitive to UV, develop skin cancer- young age
What is HNPCC
Hereditary non-polyposis colon cancer syndrome- associated w./ colon carcinoma- (germline mutation)
