Causes and Risk Factors Flashcards
How many cancers in the UK are estimated to be preventable? Can the cause be identified once diagnosed? 11:56
- 42%
- Usually not possible to identify the precise cause for individual cause
What are the preventable risk factors for cancer?
- Smoking
- Diet
- Exercise
- Infection
- Pollution
- Alcohol
(Lifestyle/environmental)
What types of mutation can occur that may result in cancer?
Permanent change in DNA sequences (passed from cell to cell):
- Single nucleotide changes/point mutations (most common)
- Insertions/deletions/amplifications
- Chromosome rearrangements/losses/gains
What are the common mutagens that may lead to cancer?
Usually carcinogens:
- Tobacco
- UV
- IR (ionising radiation)
- Chemotherapeutics drugs
What conditions increase cell proliferation, and thus in turn increase the rate of tumour progression (i.e. tumour promoters)? What do they have in common?
- Inflammation (esp. chronic, e.g. from asbestos)
- Alcohol
- Chemical promoters
- Menstruation
»> Increase cell proliferation WITHOUT changes in gene sequences
How is chronic inflammation a major risk factor in cancer?
Promotes mutagenesis
- ROS, RNS (Nitrogen); produced during inflammation; to combat pathogens, but damages self too
Promotes tumour progression
- NF-kB induces cytokines (TNF-α, IL-1 etc.); prevents apoptosis (tipping balance towards proliferation)
Promotes metastasis
- Activated neutrophils secrete TNF-α; tumor necrosis factor (causes apoptosis as well)
- Angiogenesis & migration
What effect do ROS/RNS typically have once released during inflammation?
- Oxidised bases and abasic sites (apurinic, apyrimidinic, AP)
- Single strand breaks and double strand breaks can also occur
»> If not repaired and cell does not apoptose = mutation
Describe smoking as a risk factor for cancer.
- Biggest avoidable/preventable cause
- 20X increased risk of lung cancer
- > 60 chemicals that damage DNA
» P53/KRAS (signal transduction protein downstream; RAS?) G > T change can encode different DNA, telling cells to proliferate
How does benzo(a)pyrene from smoking contribute towards cancer?
- Itself not carcinogenic
- But converted to epoxide inside cell
»> Can lead to detrimental point mutation if not apoptosed
How is infection implicated in cancer risk? Give examples.
- 16% caused by infection; 3% in the UK, >30% in sub-Saharan America
- Viruses, bacteria, animals
E.g.:
• H. pylori
• HPV (cervical)
• HCV, HBV (hepatic)
• EBV
• Herpes Type B
• Parasitic flatworms
• HTLV-1
How do oncoviruses (e.g. HPV, HCV, HBV) cause cancer?
HPV (human papilloma virus)
- 70% of cervical cancer cases
- Produces oncogenic proteins E6 & E7; interfering w/host cell proliferation signalling
»> E6 targets p53 for degradation (ubiquitination?)
»> E6 inhibits Rb (phosphorylates?)
HCV, HBV (hepatitis C/B virus)
- Inflammation (cirrhosis; of the liver)
How does H. pylori infection contribute to cancer risk?
Helicobacter pylori (bacterium)
- 50% of world’s population infected
- Gastric & duodenal ulcers (inflammation; risk)
- Increases ROS and RNS in stomach; free radicals DNA damage; mutation
»> Associated w/gastric carcinoma and mucosa associated lymphoid tissue (MALT) lymphoma
How do parasites cause cancer?
Flatworms, tapeworms (and their eggs) can cause inflammation:
- Schistosoma haematobium (flatworm) infection; bladder cancer
- Opisthorchis viverrini (flatworm); bile duct cancer
- Tapeworms in other mammals e.g. cats
- Malaria (protozoa) associated w/Burkitt’s lymphoma
What are transmissible cancers?
- Dogs and tasmanian devils can spread cancers by contact (though some of the animal population has developed resistance)
- Transmitted during surgery e.g. if surgeon exposed
What types of ionising radiation are there? How do they cause cancer? Give examples.
Can dislodge electrons:
- Alpha emitters (H+ nucleus e.g. radon-222; accumulates in basements of buildings; colourless, odourless gas)
- Beta emitters (high energy electrons, emitted from nuclei e.g. potassium-40)
- Gamma radiation (high frequency EM radiation emitted from decaying nuclei e.g. potassium-40 AGAIN)
- X-rays (not as high frequency EM radiation from e-)
- Cosmic radiation (v. high energy charged particles from space; atmosphere gives protection
(UV radiation - lower energy, mostly non-ionising)
