Biology 5 - Causes and Risk Factors (Keith Spriggs) Flashcards
What percentage of cancers are preventable?
42%
What are the initial, obviously preventable causes of cancer?
Smoking, diet, exercise, infection, pollution, alcohol
What is risk factor I?
Mutation
How can a ‘mutation’ lead to permanent change to DNA sequence?
Single nucleotide changes (most common)
Insertions, deletions, amplifications
Chromosome rearrangement, loss or gain
Mutagens are usually carcinogens
What examples of carcinogens are there?
Carcinogens often cause mutations that lead to cancers;
Tobacco, UV, IR, chemotherapeutic drugs
After initial mutation (risk factor I), which other factors can worsen cancer?
Alcohol, hormonal changes, inflammation etc
They do not cause cancer but can increase proliferation after mutation.
What is risk factor II?
Tumour promoters
How do tumour promoters cause cancer?
Once a mutation has been initiated (or several have occurred), conditions that increase cell proliferation, can go on to increase tumour progressions; e.g. inflammation (asbestos), alcohol, chemical promotors, menstruation
How does chronic inflammation present as a major cancer risk?
Promotes mutagenesis
Reactive oxygen/nitrogen species are released from inflammatory mediators that are designed to destroy pathogens but instead damage DNA.
Promotes tumour progression
NF-kB (transcription factor) induces cytokines, prevents apoptosis
Promotes metastasis
Activated neutrophils secrete TNF (tumour necrosis factor) leading to angiogenesis and migration
How does inflammation promote mutagenesis?
Reactive O2 and N2 species are released from inflammatory mediators that are designed to destroy pathogens but instead damage DNA.
How does inflammation promote tumour progression?
NF-kB (a transcription factor) induces cytokines that inhibits apoptosis
Increased cell survival
How does inflammation promote metastasis?
Activated neutrophils in the inflammatory response, secrete TNF and lead to angiogenesis and migration
How do ROS and RNS cause damage to DNA?
Typically lead to oxidised bases and abasic (apurinic and apyridiminic, AP sites)
Single strand breaks and double strand breaks can also occur
What are the roles of BER and NER?
Base and nucleotide excision repair
Without them in a cancerous cell - ROS and RNS can lead to the oxidation of bases that isn’t repaired and so goes on the lead to genomic instability and then cancer.
What is the biggest avoidable cause of cancer?
Smoking
20+% increased risk of lung cancer
p53 and KRAS mutations (KRAS is downstream signalling of EGFR)
What kinds of infection can lead to cancer?
Virus, bacteria, animals
H. pylori, HPV, EBV, parasitic flatworms etc
How do viruses cause cancer?
HPV Human Papilloma Virus (Responsible for 70% cervical cancer cases)
Produces oncogenes E6 and E7
E6 targets p53 (transcription factor) for degradation
E7 inhibits Rb (tumour supressor)
How can Helicobacter pylori cause cancer?
Bacterium
Lives in the stomach
-50% of the worlds population are infected
Causes gastric and duodenal ulcers (inflammation)
Increases ROS and RNS in the stomach
Associated with gastric carcinoma and mucosa associated lymphoid tissue (MALT) lymphoma
How do parasites cause cancer?
Flatworms, tapeworms (and their eggs) can cause chronic inflammation.
Schistoma haematobium (flatworm) infection is associated with bladder cancer
Opisthorchis viverrini (flatworm) infections is associated with bile duct cancer
Tapewormsin other mammals but not human cancer
What is the link between Malaria (protozoa) and cancer?
Associated with Burkitt’s lymphoma
What kind of cancers are transmissable?
Tasmanian devils and dogs can spread some cancers by contact
Cancer can also be transmitted through surgery (if surgeon is cut)
How can ionising radiation cause cancer?
Dislodges electrons
- Alpha emitters (H+ nucleus e.g. radon 222
- Beta emitters (high energy electrons emitted from nuclei e.g. K 40)
- Gamma radiation (high frequency electromagnetic radiation emitted from decaying nuclei K 40 again)
- x-rays (not such high frequency radiation emitted from electrons
Cosmic radiation - very high energy charged particles from space (passes straight through atmosphere)
Compared to ionising radiation, what is the energy of ultraviolet radiation like?
Primarily from sunlight (lower frequency than x-rays so not ionising)
How does ionising radiation cause damage to DNA?
Causes damage directly; double strand breaks
OR it can produce radicals which attack DNA.
How does UV radiation cause damage to DNA?
UV causes cyclo-pyrimidine dimers (Cs and Ts) and 6-4 photoproducts between adjacent pyrimidine bases
What ‘other’ environmental mutagens are potential causes of cancer?
Occupational chemicals / waste products (normally controlled to reduce exposure and prevent accidental release).
What occupational chemical can cause bladder cancer?
Aromatic amides
What occupational chemical can cause leukaemias?
Benzene
What occupational chemical can cause mesothelioma?
Asbestos, carbon nanotubes
What natural products can cause cancer if prolonged exposure to them?
Fungi - fungal toxins
Liver cancer is associated with chronic exposure
What are medical mutations?
Chemotherapy drugs; radiotherapy, x-rays, diagnostic imaging, herbal products (e.g. Aristolochia; betel nut and oral cancer)
What atmospheric particles are associated with cancer?
Vehicle exhausts; PM10s associated with lung cancer that come from diesel vehicles
What is a good diet?
Mediterranean diet
What are HCAs and when are they produced?
At high temperatures when cooking meat (red meat bad)
Heterocyclic amines
How does alcohol cause cancer?
-4% of all cancers caused by alcohol
Possible acetaldehyde is mutagenic
Liver cancer in heavy drinkers
Oral and pharangeal in smokers that drink alot also (irritant –> tumour promotion)
What are the health benefits of fibre?
Associated with reduced colorectal cancer risk
What is exercise associated with?
Reduced risks for many cancers
How can stress effect risk factors associated with cancer?
Raised corticol levels (immune suppression so more at risk from viral or bacterium)
Night working - disruption of circadian gene regulation
When can obesity be a particularly pertinent risk factor?
In post-menopausal women
How does reproduction affect the risks of breast and ovarian cancer?
Lower estrogen and progesterone exposure, reduces the risk of breast and ovarian cancer.
Which mutations can be inherited by offspring that pre-dispose the individual to breast cancer?
BRCA1 and BRCA2
When can mutations be passed onto offspring?
Only when the mutation occurs in germ cells
Cancer is normally genetic but is less often inherited
How can cancer occur by chance?
Mistakes happen in DNA replication - 1 in 10^9 nucleotides
Even if the rate of error is low, the frequency of DNA replication is so high, errors accumulate.
What happens in our body when one base if modified?
One base modification is enough to trigger P53 which causes cell cycle arrest and repair or apoptosis
