7. causes treatment and prevention of cancer

Question 1

what are the three causes of cancer?

Answer 1

• Carcinogens
• Infectious agents
• Inherited predisposition

Question 2

How do carcinogens cause mutations?

Answer 2

• Reaction with free radicals
• Mechanisms of mutation, 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
  • The more double stranded breaks (associated with high level radiation) more likely the repair will have mistakes
  • Environmental toxins will add bases- DNA repair mechanism don’t recognise/ mis read base
  • These don’t get inherited, the mutation gets inherited
  • Diet is a major source of carcinogen ( as well as obesity due to changes in chemical signals)

Question 3

infectious agents and cancer

Answer 3

chronic inflammation promotes cancer

Question 4

Inherited Cancer Predispositions

Answer 4

• Principle: inherited mutation in a gene causing a defect in the machinery that guards against genome damage, either monitoring or DNA damage repair
• E.g. Li Faraumini (P53); BRCA1; if P53 very strong inheritance to get cancer and recurring bottleneck areas more chance of inheriting genes

Question 5

BRCA1 and 2 genes

Answer 5

• Family history is strongest predictor of risk of breast cancer
• Mutated BRCA1 and BRCA2 genes carry 45–90% lifetime risk of breast cancer and a 40–60% risk of ovarian cancer.
• People of Ashkenazi Jewish descent are at a much higher risk (as many as 1/40 carry the mutated gene)
• BRCA genes responsible for 2-10% of breast cancer cases
• BRCA isn’t sporadic (regulatory gene) - other genes involved
• They normally help in DNA repair, so when they are defective, tissue is more prone to the consequences of DNA damage

Question 6

Screening programmes

Answer 6

• Breast
• Cervical
• Colon

Question 7

Cancer screening

who can be screened?

Answer 7

• Never population wide: at risk groups
• By age:enough cases to screen this pop. to pick it up early
  
  • Breast – 47-73yrs
  • Colon – 60-74yrs
  • Prostate – 50 plus
  • Cervical 25-65yrs
• By genetics:
  
  • BRCA1 – breast (also ovarian)
    
    • Women with mutated BRCA1 gene
    • Offered screening if known to be in a family or ethnic group with this predisposition.
    • Offered mastectomy
• Families with known genetic inheritance also screened for colon, kidney, pancreatic…

Question 8

breast cancer screening

Answer 8

X-ray based mammography

BUT, many would not progress to a life-threatening cancer during the lifetime of the women - not aggressive or death from another cause

It is now estimated 3 cases over-diagnosed for every 1 life saved.

Question 9

Cervical cancer: screening

Answer 9

20 and 30 years age. Pap smear. Recently replaced by ‘liquid based cytology’ (LBC), works because the normal cells of the cervix are relatively uniform.

Developed countries, mortality now 70% lower than 30 years ago. Recently added detection of the HPV virus that causes the cancer.

Question 10

Bowel cancer screening

Answer 10

• ‘Foecal occult blood test’ (FOBT) stool sample and look for blood suggesting bleeding in bowel
• Colonoscopy shown to detect 4-5x more polyps and cancers than the FOBT.

So why not adopt colonoscopy as the method of initial screening?

Much cheaper and better patient adherence

Eg. Not as many people go for colonoscopy

Question 11

Radiotherapy:

how is the damage limited

how do cells die

Answer 11

therapy targets the tumour

• ‘fractionated’ pulses- normal cells can recover
• ‘brachytherapy’ pellets of radioactive material planted into tumour.

Cancer cells that survive therapy are very difficult to treat

Want to find some non-carcinogenic therapies

Genome becomes progressively more damaged until it is insufficiently intact to continue and they die from ‘mitotic catastrophe’.

Free-radical generated by therapy can also damage other components of the cell, such as cell membrane proteins, which can also trigger apoptosis by alternative pathways.

Question 12

Chemotherapy:

Answer 12

systemic, toxic

Question 13

what are targeted therapies

Answer 13

Therapies based on known features of cancer cells:

• Antibodies to specific antigens Not powerful enough, become resistant and have side effects
• Small molecule inhibitors block oncogene
• Angiogenesis inhibitors
• Immune system booster, vaccines..etc… these work by
  
  • Getting IS to recognise tumour and attack
  • Stopping IS being switched off and recognising signals released by tumour to attack it

Question 14

Prevention of cancer

lifestyle cannot cure it

Answer 14

• Lifestyle- smoking, UV, processed meat
• Immunisation- HPV, hepatitis
• Prenatal genetic diagnosis
  
  • IVF, choose the embryos without cancer gene and reimplant

Question 15

other potential causes of cancer

Answer 15

immune suppression

food types

tissue growth in kids

hormomes: breast feeding when younger and for longer periods have lower chances of cancer- due to hormones