molecular basis of breast cancer Flashcards
what is BRCA gene
dominant not completely penetrant (risk is not 100%) large gene mutation can occur anywhere on the gene mostly truncated proteins as a result
what is BRCA1
tumour suppressor gene
DNA damage repair
similar to BRCA2
recognises the DNA break
what is the knudson hypothesis
two hit hypothesis
what is the BRCA2 gene
truncated protein
increases risk of prostate cancer
many possible mutations, not all are significant
binds to RAD51 protein
responds to DNA damage. promotes exchange of strands
BRCA2 deficient cells are sensitive to DNA damage
what factors should be considered in referral to genetic counselling
no. of family members affected
what generations
age on onset
ethnic background
breast cancer is often polygenic so difficult to give information
what can we do to reduce the risk for people diagnosed with BRCA mutations
tamoxifen
mastectomy
oophorectomy
oral contraceptives
why do BRCA genes affect the breast
possibly due to oestrogen metabolites
what is synthetic lethality
two gene mutations together cause cell death
could be used to treat cancer
what is PARP (poly ADP ribose polymerase)
repairs ss DNA breaks
PARP inhibitors could be used to target tumour cells only because they have the BRCA mutations
however resistance can arise
what proportion of tumours are oestrogen receptor positive
60%
what is tamoxifen
prodrug
oestrogen receptor antagonist
prevent expression of genes which would otherwise be stimulated by oestrogen
however causes early menopausal symptoms
what are the risk factors for sporadic breast cancer
early menarche
late menopause
first child after 30
what is HER2/erbB2
epidermal growth factor receptor
over expressed in 20-30% of tumours
causes gene amplification and cell division
what is Herceptin/ Trastuzumab
humanised monoclonal antibody to HER2 Prevents signalling suppresses growth and angiogenesis cell mediated cytoxicity selectively targets the extracellular domain of the HER2 protein
tells your body to target the cancer cell
prevents the cell from signalling so can’t grow
what part of cell division checks for aneuploidy
the mitotic checkpoint
