T5 Tumours Flashcards
what are the three types of differentiation in tumour?
- well-differentiated
- moderately
- poorly
anaplasia
poorly differentiated neoplasm; highly pleomorphic
most common cancers in males & females
- (prostate or breast)
- lung
- bowel
most mortal cancers in the UK
- pancreas
- brain
- lung
- oesophagus
- stomach
what are the effects of 1ry tumour?
- bleeding
- obstruction
what are the effects of distant metastases?
cancer spreading
what are the causes of paraneoplastic syndromes?
- proteins secreted by tumour
- immune cross reactivity
classification of tumours
(see week 5 summary notes)
what effect fo initiators have on DNA
- genotoxic –> chemically modify it
what is the effect of promoters
induce proliferation; DNA replication
in a mutation, what causes the gain of function?
activation of proto-oncogenes
in a mutation, what causes the loss of function?
inactivation of tumour suppressor
how is tumour suppressor gene inactivated?
- methylation
- CpG islands
what are the direct acting chemicals causing mutation?
- free radicals
- nitrosamines
- UV light
- ionising radiation
what do procarcinogens require before ractoing with DNA?
enzymatic activation
give examples of procarcinogens
- aromatic amines
- polycyclic aromatic hydrocarbons (PAHs)
DNA damage & repair mechanisms
check out summary notes
what enzyme can detoxify/excrete carcinogen? (might be why not all exposures lead to cancer)
glutathione S-transferase
what cancers is alcohol associated with?
- oral
- oesophageal
- bowel
- liver
what does alcohol casue that can lead to cancer?
- acetyldehyde formation
- +++ oestrogen & testosterone
- +++ carcinogens uptake (esp. in GI cells)
- — folate (needed for accurate DNA replication)
- kill surface epithelium
cancers associated with chronic inflamamtion
- HBV
- HCV
why does inflammatory response increase the risk of cancer?
- free radicals –> DNA damage
- growth factor repairing tissues –> promotor
sporadic vs inherited cancer in terms of Kundson’s two hit hypothesis
- sporadic: two hits required
- inherited: one hit required
(autosomal dominant pattern of inheritence
function of gatekeepers
- directly regulate tumour growth
- monitor & control cell division & death
- preventing accumulation of mutations
function of caretakers
- improve genomic stability: repair mutations
function of landscapers
- control surrounding stormal environment
examples of TSG
- APC
- BRCA1/2
- TP53
- Rb
function of oncogenes
- regulate cell growth /differentiation
examples of oncogenes
- growth & signal transduction factors
- RET genes
compare the difference between the effect of gain/loss of function on the risk of cancer
- TSG: loss of function –> +++ cancer risk
- onco: gain of function –> +++ cancer risk
examples of autosomal recessive conditions
- MUTYH associated polyposis
- Fanconi anaemia
- Alaxia telangiectasia
(can increase risk of sporadic cancer)
compare sporadic to familial cancers:
sporadic: old onset; one cancer in individual; unaffected fam; rarely genetic cancers
familial: young onset; multiple cancers; fam affected; genetic cancers
diagnostic vs predictive testing
- diagnostic: DNA from affected relative to identify mutation
- predictive: testing for mutation in affecetd individuals’ relatives
what cancer is associated with Lynch syndrome
- bowel
- endometrial
- ovarian
- stomach
- urinary tract
what is the inheritance pattern for breast cancer and lynch syndrome
AD
which mismatch repair genes are affected in Lynch syndrome
- MLH1
- MLH2
- MLH6
- MLH2
