17. Causes of Cancer Flashcards
how are human carcinogens identified?
- geographical variance in risk
- occupational exposure
- accidental exposure
- big epidemiological surveys
- laboratory experiments
what are the categories of human carcinogens?
chemicals infectious agents radiation minerals physiological chronic inflammation
what tissues does alcohol affect?
pharynx, larynx, oesophagus, liver
what tissues does asbestos affect?
lung, pleura
which carcinogen affects the bone marrow?
x rays
which carcinogen affects the skin?
UV light
which carcinogen affects breast tissue?
Oestrogen
which tissues does tobacco smoke affect?
mouth, lung, oesophagus, pancreas, kidney, bladder, etc.
which carcinogens affect the liver?
Aflatoxin and Hep B
which carcinogen affects the cervix?
HPV
what is a carcinogen?
any agent that significantly increases the risk of developing cancer
what are the 3 functional types of carcinogens?
- initiators
- promoters
- complete
how do initiators work?
can chemically modify or damage DNA (genotoxic). 2 steps -
- chemical modification of DNA
- replication of modified DNA and mis-incorporation by DNA polymerase
how do promoters work?
non genotoxic
induce proliferation and DNA replications either
a. stimulate 2 rounds of DNA replication required for mutation fixation
b. stimulate clonal expansion of mutated cells, enabling accumulation of further mutations
how do complete carcinogens work?
they can both initiate and promote
how does tissue progress from a mutation to cancer?
- genotoxic initiating agent damages DNA
- promoting agent fixes damage as a mutation and converts normal cell into mutant initiated cell
- promoting agent stimulates clonal expansion of initiated cell to produce papillomas
- further rounds of mutation and clonal expansion allows the papilloma to progress into a carcinoma
what are the common genetic abnormalities seen in cancers/
base pair substitutions frameshift deletion gene amplification chromosomal translocation chromosomal inversion aneuploidy
which is the most common way of inactivating tumour suppressor genes?
methylation
what are the functional consequences of mutation?
mutations in oncogenes lead to a gain of function
mutations in TSGs lead to a loss of function
how are carcinogens classified according to metabolic activation?
- direct acting - interact directly with DNA
2. pro carcinogens - require enzymatic activation before they react with DNA
what are the steps in the metabolic activation of benzopyrene?
- benzopyrene
- benzopyrene 7,8-epoxide
- benzopyrene 7,8- dihydrodiol
- benzopyrene 7,8-diol, 9-10-epoxide (BPDE)
which process are in place to repair damaged DNA?
base excision repair
nucleotide excision repair
recombinational repair
mismatch repair
what protective mechanisms does the body have in place to prevent cancer?
- prevention of metabolic activation of the carcinogen
- dietary antioxidants
- detoxification mechanisms
- DNA repair enzymes
- apoptotic response to unprepared genetic damage
- immune response to infection and abnormal cells
how many carcinogens does tobacco smoke have?
19
why is alcohol considered a carcinogen?
- converted to acetaldehyde in the liver, can cause DNA damage
- increases levels of oestrogen and testosterone
- increases uptake of carcinogenic chemicals into cells within the upper GI tract
- reduces levels of folate
- kills surface epithelium, leading to unscheduled proliferation
why is oestrogen considered a carcinogen?
it can both stimulate cell division and induce DNA damage
how does chronic inflammation play a role in cancer?
- DNA damage from release of free radicals by immune cells - initiation
- growth factor induced cell division to repair tissue damage - promotion
examples of inflammatory diseases associated with cancer
colitis hepatitis barrett's metaplasia gastritis gallstones
