Causes of Cancer: Genetic Flashcards
(19 cards)
define cancer
fully developed tumour with a capacity to invade and destroy surrounding tissue, and spread to distant sites
Cancer cell morphology VS normal cell
- cancer:
- loss of contact inhibition and uncontrolled proliferation
- increase growth factor secretion
- increase in oncogenic expression
- loss of TSG function
- neovascularisation
- Normal:
- oncogenic expression rare
- intermittent/coordinated gf secretion
- presence of TSGs
Factors in getting cancer
- age
- sex
- radiation
- chemotherapy
- genetics
- environment/lifestyle
- endocrine
- medical complications (infection)
most common cancer in men
prostatic
highest mortality cancer in men and women
lung
most common cancer in women
breast
why is oesophageal cancer increasing
treatment for H pylori causes acid reflux, leading to changes in epithelium of oesophagus
multistep process
initiation: carcinogen induces changes in cells, but still phenotypically normal. initiated cells are latent until acted on by a promotor/further initiation event
eg. chemical carinogens, ciruses, radiation, replication errors,
promotion: promote growth of a tumour, creating more changes
eg. inflammation, hormones, growth promotors
monoclonal tumours
- cells within a given tumour descend from a single cell
- most tumours are monoclonal BUT heterogenous due to continuous evolving of different cells
- evolution occurs in a branching fashion, leading to extensive hereogeneity
polyclonal tumours
- tumours originating from multiple cells
- (eg. tumours originating from transforming RNA tumour viruses, other infectious agents (they can spread) and hereditary cancer syndromes bc initiating event is very common)
epigenetics
- epigenetic changes can also induce cancer
- switching off of promoter by methylation events
- so gene is knocked out
- important in TSGs
how does cancer form with slow mutation rate?
- initiator events often DNA damage repair genes
- increase genetic instability
- eg. Lynch syndrome defect in MMR
- eg. XP defect in NER
aneuploidy
defective mitotic checkpoints
leads to aberrant numbers of chromosomes
level of aneuploidy important in cancer survival
Down syndrome and cancer
- three copies of 21
- very low risk of solid tumours
- increased risk of blood cancer risk
examples of commonly amplified genes
- c-myc (neuroblastoma)
- cyclin D1
- erbB1
- cab1
example of common translocations
- BCR:ABL1 (CML, ALL)
- gleevec treatment
p21
- inhibits kiase activity of cyclin/CDK complexes
- stops phosphorylation of RB1
- cell cycle arrest
common TSGs
- VHL (renal)
- APC (CRC)
- p53
- RB1
multistep carcinogenesis
order of accumulation is important in tumourigenesis
- vogelsteins CRC progression
