Carcinogenesis - Causes of Cancer (20) Flashcards
Chemicals
PAHs, nitrosamines
Infectious agents
HPV, H.pylori
Radiation
UV light, radon
Minerals
Asbestos, heavy metals
Physiological
Oestrogen, androgens
Chronic inflammation
Free radicals and growth factors
What tissue does Aflatoxin cause cancer in?
Liver
What tissue does Alcohol cause cancer in?
Pharynx, larynx, oesophagus, liver
What tissue does Asbestos cause cancer in?
Lung pleura
What tissue do X-rays cause cancer in?
Bone marrow (leukaemia)
What tissue do UV-light cause cancer in?
Skin
What tissue does Oestrogen cause cancer in?
Breast
What tissue does Tobacco smoke cause cancer in?
Mouth, lung, oesophagus, pancreas, kidney, bladder
What tissue does HBV cause cancer in?
Liver
What tissue does HPV cause cancer in?
Cervix
Carcinogen
Agent that significantly increases risk of cancer
Initiators
Carcinogens often genotoxic - chemically modify/damage DNA
Promoters
Carcinogens that induce proliferation and DNA replication
What is a complete carcinogen?
Can initiate and promote e.g. UV light
Initiation requires
Chemical modification of DNA and replication of modified DNA and mis-incorporation by DNA polymerase
Promotion
Stimulate two rounds of DNA replication required for mutation fixation and stimulate clonal expansion of mutated cells
Common genetic abnormalities
Base pair substitution, frameshift, deletion, gene amplification, chromosomal translocation, chromosomal inversion, aneuploidy
DNA methylation in tumours
Often inactivates tumour suppressor genes
Mutations in oncogenes
Base pair substitutions, amplification, translocations, inversions
Mutations in TSGs
Base pair substitutions, frameshifts, deletions, insertions, chromosomal rearrangements, chromosome loss, promoter methylation
Direct acting metabolic activation
Interact directly with DNA e.g. oxygen radicals, nitrosamines, UV light, ionising radiation
Metabolic activation - procarcinogens
Require enzymatic (metabolic) activation before they react with DNA e.g. aromatic amines, polycyclic aromatic hydrocarbons (PAHs)
Metabolic activation of benzopyrene
(Pro-Carcinogen) BPDE active
Defence against carinogenesis
Exposure to myriad carcinogenic agents, many levels of defence, dietary antioxidants, detoxification mechanisms, DNA repair enzymes, Apoptotic response to unrepaired genetic damage, Immune response to infection and abnormal cells
Tobacco smoke
19 carcinogens (benzopyrene, acrolein, nitrosamines, radioactive lead and polonium, cadmium, chromium), X100 increased risk of head and neck cancer
Alcohol is linked to which cancer?
Oral, oesophageal, pharynx, larynx, breast bowel and liver cancer
How does alcohol cause cancer?
Converted into acetaldehyde (cause DNA damage), increases levels of oestrogen and testosterone, increases uptake of carcinogenic chemicals into cells within upper GI, reduces levels of folate (accurate DNA replication), can kill surface epithelium > unscheduled proliferation
Oestrogen
Stimulate cell division and induce DNA damage, binds to transcription factors (breast cancer)
Chronic inflammation is associated with which cancers?
Colitis, hepatitis, Barrett’s metaplasia, gastritis, gallstones
How does chronic inflammation cause cancer?
DNA damage from release of free radicals by immune cells (initiation) and growth factor induced cell division to repair tissue damage (promotion)
