Causes and epidemiology of cancer

• Describe the principles of cancer diagnosis

  • Clinical presentation: observation of symptoms and signs suggestive of cancer.
  • Biopsy: remove of tissue for microscopic examination to confirm the presence of cancer
  • Imaging studies: X-rays, MRI, CT scans and PET scans
  • Laboratory tests: blood tests to detect elevated levels of cancer markers and abnormal cells
  • Staging: determination of size and spread of the cancer
  • Prognosis: prediction of the likely outcome of the disease
• Describe the change in cancer cell glucose metabolism

  Cancer cells shunt energy production to glycolysis only, which results in a higher use of glucose. This is via activation of the Ras MAPK and AKt PI3K pathway. Akt drives the expression of GLUT1; a glucose transporter. PI3K activates HIF1, which turns off PDH and inhibits the citric acid cycle.
• How can we utilise the altered energy production in cancer in diagnosis?

  FGD-PET scans visualise tumours that have concentrated large amounts of glucose due to hyperactivity og the GLUT1 transporter. This allows us to identify smaller masses earlier on. However, the drawback of this is that there are many false positives or identification of small benign masses, which can be harmful as treatment may cause more side effects than just leaving the patient As they were.
• How does alcohol cause cancer?

  As the body breaks down alcohol creates toxic by-products, including acetaldehyde, which can damage DNA and proteins in cells and increase the risk of cancer. Alcohol can also increase hormone levels, such as oestrogen, which stimulates the growth of certain cancers, such as breast cancer. Furthermore, alcohol leads to inflammation, oxidative stress and weakens the immune system. However, these are reversible and concentration dependent.
• How does smoking cause cancer?

  Cigarette smoke releases harmful chemicals into our lungs that cause damage to out DNA, including genes the protect against cancer. Some chemicals make it harder for cells to repair DNA damage.
• How can obesity cause cancer?

  • Chronic inflammation: fat cell removal can lead to chronic inflammation
  • Insulin resistance: leads to higher levels of insulin and insulin-like growth factors in the blood
  • Hormonal alterations: levels of hormones like oestrogen and testosterone
  • Organ pressure: leads to structural changes and build up of waste products
  • Poor nutrition
• Describe the structure of carcinogens and mutagens

  These molecules usually contain benzene rings which mimic biological molecules, such as amino acids. This allows them to be integrated into metabolic pathways and cause failures. Some of these are only active after processing in liver.
• Describe the AMES test

  1. Rat liver is homogenised and used to metabolically activate the test compound by rat liver enzymes.
  2. The metabolically activated compound is added to salmonella bacteria that is unable to grow without added histidine in culture medium.
  3. Count the number of bacterial colonies that have undergone mutation enabling them to grow without added to hisitidine.