causes, treatment and prevention of cancer Flashcards
causes of cancer
- carcinogens
- infectious agents
- inherited predisposition
hoe do carcinogens cause mutations?
- Reaction with free radicals (radiation)
- Mechanisms include adducts, cross links, breaks etc.
- Increase the rate of mutation, DNA breaks or base changes
- Lead to errors such as incorrect bases incorporated or mis-joining of chromosome ends
infectious agents
mechanisms: 1) inflammation cure with antibiotics 2) inflammation and genes acute = hepatitis; chronic = cancer 3) oncogenes vaccination 4) oncogenes glandular fever and cancer (incidence coincides with malaria) 5) immune suppression control with antivirals 6) intrinsic causes- tissue growth (developmental). hormones (prostate and breast)
infectious agents: vaccination
- Since 2008 12–13-year-old-girls in the UK have received a vaccine against four HPV variants
- The first cohort immunized are now 24-25 years old (the age at which screening starts)
- From Sep-2019 all 12-13 year old’s are eligible
inherited cancer predispositions
Principle:
An inherited mutation in a gene that causes a defect in the machinery that guards against genome damage (either monitoring or DNA repair)
e.g. Li-Fraumeni syndrome (p53; multiple cancers)
BRCA1 (breast cancer)
BRCA1 and BRCA2 genes
Family history is strongest predictor of risk of breast cancer
BRCA genes responsible for 2-10% of breast cancer cases
They normally help in DNA repair, so when they are defective tissue is more prone to the consequences of DNA damage
Mutated BRCA1 and BRCA2 genes carry 45–90% lifetime risk of breast cancer and a 40–60% risk of ovarian cancer.
1:150-800 of Western women inherit these mutations (UK 1/450)
People of Ashkenazi Jewish descent are at a much higher risk (as many asone in 40 carry the mutated gene).
Breast cancer:1,700,000 cases, 500,000 deaths worldwide each year
BRCA1
• involved in breast and also ovarian cancers
• Women offered testing if known to be in a family or ethnic group with this predisposition
• If mutated BRCA1 gene then offered mastectomy
Families with known genetic inheritance also screened for colon, kidney, pancreatic cancers (requires that markers of genetic predisposition are known)
screening programmes: breast cancer
X-ray based mammography from 1970-80s saves around 1,400 lives per year in UK
However, many would not progress to a life-threatening cancer (either not aggressive or death from another cause)
Estimated 3 cases over-diagnosed for every life saved
i.e. there is a 1/200 chance screening will save a woman’s life but a 3/200 chance that treatment will be unnecessary
screening programmes: cervical cancer
Offered over age 25+ yrs.
Pap smear introduced in the 1930s by George Papanicolaou.
It has replaced by ‘liquid based cytology’ (LBC) plus HPV assay;
Pap smear works well because normal cells of the cervix are relatively uniform
UK mortality now ~70% lower than 30 years ago
screening programmes: bowel cancer
- Over 16,000 deaths / year in UK (2015-17)
- Generally starts as a slow growing precancerous mass
- Tests include faecal occult blood test (FOBT; used in UK) and colonoscopy
- Colonoscopy shown to detect 4-5x more polyps and cancers than FOBT, but 10x more cost
- Virtual colonoscopy (a CAT scan) gives 3D picture of colon and rectum
- Almost as sensitive as colonoscopy but ⅓ cost and without the associated risks (not yet used in UK)
cancer therapeutics (very briefly_
- surgery, radio- and chemo-therapy
- targeted therapies
radiotherapy
a type of cancer treatment that uses beams of intense energy to kill cancer cells.
X-rays or isotopes:
• Radiation therapy most often uses X-rays, but protons or other types of energy also can be used.
• Damages cells to such an extent they cannot survive
(equivalent to placing cancer cells less than 2km from the epicentre of the nuclear bombs dropped on Hiroshima or Nagasaki)
cancer cells more sensitive to DNA damage
• If this radiation was experienced body-wide it would kill us, but therapy targets the tumour
- fractionated. Multiple lower doses are less toxic to normal cells
- brachytherapy. Use of sealed sourcesThe seeds emit radiation that dissipates over a few months.
-three-dimensional conformal radiation therapy. 3D CRT is a geometric shaping of the radiation beam so that the fields conform closely to the shape of the tumour. Given from multiple directions.
how does radiotherapy
mitotic catastrophe.
Most dividing cancer cells initially survive, continuing to progress through the cell cycle despite the breaks in their DNA
• The genome becomes progressively more damaged until it is insufficiently intact to continue and the cells die from ‘mitotic catastrophe’
• Free-radicals can also damage other components of the cell, such as membrane proteins, which can then trigger apoptosis by alternative pathways
antimetabolites
mechanism.
various; generally interfere with DNA replication
alkylating agents
mechanism- DNA cross linking
