5 Flashcards
What are the two types of Risk with cancer?
1) Mutations Risk
2) Tumour Promoters Risk
Mutations Risk
Permanent change in DNA sequence caused by mutagens, tobaco, UV, IR, chemo
Tumour promoters Risk
Inflammation, alcohol, chemical promoters and menstruation lead to increased proliferation
How does inflammation cause cancer?
- Promotes mutagenesis: ROS, RNS are produced
- Promotes tumour progression: NF-kB induces cytokines, prevent apoptosis and increases proliferation
- Promotes metastasis: activated neutrophils secrete TNF, angiogenesis and migration.
ROS and RNS lead to oxidised bases, single and double strand breaks occur -> persistent DNA damage.
What does change in gene expression do?
Change in gene expression= chronic inflammation= persistent production of ROS/RNS.
How does smoking lead to cancer?
Leads to p53 (12th codon) and KRAS (triple of codons) mutations, by Benz(a)anthracene that is converted to epoxide in the lung and reacts with guanine in DNA, which is then misread as thymine during replication: transversion mutation.
What is the main risk of smoking?
- 20x increased risk of lung cancer
- <60 chemicals that damage DNA
How do bacteria lead to cancer?
H.pylori causes inflammation in the stomach -> ROS/RNS -> free radicals -> DNA damage; gastric carcinoma.
How do viruses lead to cancer?
HPV produces oncogenic proteins E6 and E7; E6 targets p53 for degradation and E7 inhibits Rb.
How do animals lead to cancer?
- Flatworms: bladder cancer and bile duct cancer
- Tapeworms cause inflammation
- Malaria: lymphoma
- Dogs and Tasmanian devils can spread cancers by contact
How does Ionising radiation lead to cancer?
dislodges electrons, makes molecules reactive
- > DNA damage.
- Alpha emitters (H+ nucleus)
- Beta emitters (high energy electrons emitted from nuclei)
- Gamma radiation (high frequency electromagnetic radiation emitted from decaying nuclei)
- X-rays
- Cosmic radiation (very high energy charged particles from space)
How does ultraviolet radiation lead to cancer?
lower energy; primarily from sunlight.
Causes cyclo-pyrimidine dimers and 6-4 photoproducts between adjacent pyrimidine bases.
What environmental mutagens lead to cancer?
- Occupational chemicals/waste products
- Natural products (fungal toxins)
- Medical mutagens: chemotherapy drugs, radiotherapy, x-rays, herbal products (aristolochia).
- Atmospheric particles, from exhaust, e.g. PM10s= lung cancer
How is food linked to cancer?
Fruit and veg are linked to lower risk of mouth, throat and lung cancer and fibres reduces bowel.
Processed and red meat increases bowel cancer risk.
How does obesity increase cancer risk?
Fat cells produce proliferative signals (estrogen, androgen, insulin); inflammatory signaling and recruitment of immune cells; abdominal fat partially harmful.
Why does physical activity reduce the risk?
Physical activity = decrease in insulin and estrogen + more movement through digestive system, therefore less contact with carcinogens (alcohol) + reduces inflammation and stress.
What cancers does alcohol increase risk for?
Causes 4% of Cancers
Increased risk of mouth, throat, breast, liver and bowel cancers
How does alcohol cause risk?
Converted to acetaldehyde which can damage DNA and causes inflammation; leads to ROS.
Can increase estrogen levels
How does menopause age effect BC risk?
Later menarche decreases BC risk
Earlier menopause decreases BC risk
Does pregnancy and breastfeeding increase or reduce risk of BC and O cancer?
Pregnancy reduces breast and ovarian cancer risk
Breast feeding >1 reduces breast cancer risk
How do hormone levels increase cancer risk?
Increase in progesterone and estrogen leads to cancer:
- Early menarche, later menopause, no children
- Hormone replacement therapy
- Hormonal contraceptives
Do genetics contribute to cancer risk? Give examples and why
BRAC1 and BRAC2 in breast cancer: x5 higher risk
Mutations in oncogenes and tumour suppressors only passed on if occur in germ cells.
How is ‘chance’ a risk?
1 in 109 nucleotides =mistake in DNA replication = cancer
