Lect 20 - Carcinogenesis: Causes of Cancer Flashcards
what are the Categories of human carcinogens?
Chemicals Infectious agents (H. Pylori) Radiation Minerals (heavy metals) Physiological (oestrogen) Chronic inflammation (free radicals and growth factors)
what does Aflatoxin target?
liver
what does Alcohol target?
pharynx, larynx, oesoph., liver
what does Asbestos target?
lung pleura
what do Xrays target?
bone marrow (leukaemia)
what does UV-light target?
skin
what does Oestrogen target?
breast
what does Tobacco smoke target?
mouth, lung, oesophagus,
pancreas, kidney, bladder, etc.
what does HBV target ?
liver
what does HPV target ?
cervix
what is a carcinogen?
Any agent that significantly increases the risk of developing cancer
what are INITIATORS?
Carcinogens that are genotoxic i.e. can chemically modify or damage DNA
what are PROMOTERS?
non-genotoxic Carcinogens e.g. induce proliferation and DNA replication
what are “complete” carcinogens?
carcinogen that can initiate and promote e.g. UV light
what does Mutation induction (initiation) require?
Chemical modification of DNA
Replication of modified DNA and mis-incorporation by DNA polymerase
name some Common genetic abnormalities (4)
Base pair substitution
Frameshift
Deletion
Gene amplification
what can cause tissue suppressor genes to be epigenetically under expressed?
Aberrent methylation.
what do mutations in oncogenes cause?
gain of function - amplification
what does loss of TSGs lead to?
loss of function - inability to prevent amplification
what is a Procarcinogen?
an agent that requires enzymatic (metabolic) activation before they react with DNA, e.g. aromatic amines, polycyclic aromatic hydrocarbons (PAHs)
what Defences against carcinogenesis are there?
Dietary antioxidants
Detoxification mechanisms
DNA repair enzymes
Apoptotic response to unrepaired genetic damage
Immune response to infection and abnormal cells
how many identified carcinogens are there in tobacco smoke?
19
In combination with promotion by alcohol leads to 100-fold increased risk for head & neck cancer
how does alcohol cause DNA damage?
it is converted into acetaldehyde, which can cause DNA damage.
increases levels of oestrogen and testosterone
increases uptake of carcinogenic chemicals
reduces levels of folate, needed for accurate DNA replication
can kill surface epithelium leading to unscheduled proliferation
give examples of types of chronic inflammation that are important in causing cancer.
colitis, hepatitis, Barrett’s metaplasia, gastritis, gallstones
