9 Neoplasia 3&4 Flashcards
Describe multifactorial nature of neoplasia pathogenesis
Intrinsic factors: Heredity, Age, Sex
Extrinsic factors: Environment (chemicals, radiation, infection) , Behaviour
How can overweight/obesity cause cancer
Adipose tissues can produce hormones & inflammatory molecules that contribute to the development of hyperplasia
Describe the geographical variations in the incidence of malignant tumours
Geographical regions can either be protective or carcinogenic depending on the type of cancer
E.g.) Japanese migrants to USA; ⬆️breast cancer⬇️gastric cancer
Describe the mechanism of Chemical carcinogenesis
- The presence of an initiator (non-lethal) in a neoplastic clone causes mutation
- Monoclonal neoplastic proliferation is caused by a promtoer
- Expansion of a mutated pop.
Examples of chemical carcinogens and the common cancers they can cause
2-naphthylamine: seen in dye&cigarettes, Bladder cancer
Benzopyrene: seen in cigarettes
Aflatoxin: seen in fertilisers, Liver cancer
Asbestos: seen in insulators in buildings, Mesothelioma
How can a pro-carcinogen be converted into a carcinogen
Cytochrome P450
Carcinogens can be…
Both can be an initiator & promoter (tobacco)
OR
Either initiator/promoter
Describe the mechanism of carcinogenesis caused by radiation
Alpha/beta practices, gamma rays, X-rays, UV rays can damage
-DNA directly
-Indirectly by generating free radicals
Describe the mechanism of carcinogenesis caused by infection
- Direct effects (e.g.HPV)
- Indirect effects (e.g.Hep B) ➡️ chronic liver cell injury & regeneration
- Reduced Immunity (HIV)
Describe how HPV (Human Papilloma Virus) can affect genes that control cell growth
Associated with cervical carcinoma
-HPV makes 2 proteins (E6 & E7)
- Virus infects cell, causes further replication of virus particles without killing the cell
Method: E6 inhibit p53 which prevents cell from undergoing apoptosis - Interfering with Retinoblastoma protein which is important as a cell cycle checkpoint
Describe the functions of Proto-oncogenes
Give an example
Participate in signalling pathways that drive proliferation
-mutations that activate these cause an excessive increase in one/more normal functions
‘Gain-of-function’ mutations
E.g.) RAS
What is a RAS gene and how is it involved in neoplasia
-Most common type of abnormality involving proto-oncogenes in human tumours
- Point mutation in RAS meaning there is no need for a growth factor for RAS to bind to GTP
Describe the function of Tumour Suppressor Genes
Give an example
Stop cell proliferation
-in most instances both alleles must be damaged for transformation to occur
-abnormalities in these genes leads to failure of growth inhibition
E.g.) Retinoblastoma, p53
Describe the functions of DNA repair genes in neoplasia
Give an example
‘Caretaker genes’
-repairs DNA mutation
Some inherited cancer syndromes have germline mutations that cause malignant neoplasm
E.g.) Xeroderma Pigmentosa (autosomal recessive)
-mutation gene that affects DNA nucleotide excision repair
Describe the stages of carcinogenesis
- Somatic cells are exposed to env. carcinogens that are either initiators/promoters gowing in a monoclonal pop. of mutant genes.
- Some of the clones harbour mutations affecting a proto-oncogene/tumour suppressor gene, affecting hallmark changes
- During progression, the cells acquire further activated oncogenes/inactivated tumour suppressor genes
- This eventually results in a pop. of cells that have acquired a set of mutations that produce all of the hallmarks of cancer