Chapter 4

Summary of the science so far, and some clinical predictions

Skin cancer is the result of UVR causing mutations in either keratinocytes or melanocytes. Acute exposure to UVR causes erythema via DNA damage and sets in motion a number of protective strategies such as tanning and epidermal thickening designed to minimise damage from further ultraviolet radiation. Failure to repair all the ultraviolet radiation induced mutations leads in the long term to cancer. UVR may also increase the risk of cancer because UVR may be a tumour promoter and because it interferes with normal immunosurveillance.

We can make testable predictions about what will be the key determinants of cancer incidence.

  1. Age: Age is a proxy for exposure to UVR and the older a person the greater the cumulative UVR exposure, and therefore the more mutations and other harmful effects of UVR.
  2. Exposure to UVR: persons living in areas with high ambient UVR will —all other factors being equal—have higher cancer rates, and body sites that are most exposed to UVR have the highest cancer rates.
  3. Pigmentation: Melanin protects against UVR. Those with pale skin, whether reflecting natural variation in skin colour or due to disorders such as albinism, will show higher cancer rates.
  4. Behaviour: Whatever the ambient UVR levels, persons who spend greater time outdoors will have higher cancer rates
  5. Inherited syndromes in tumour suppressor genes will predispose to cancers at a younger age
  6. Patients receiving certain immunosuppressive drugs will show an increase in cancer rates.
  7. People with defects in DNA repair (or other forms of cellular protection against UVR) will increase skin cancer rates.
  8. Mutagens other than UVR that affect skin cells will increase cancer rates

In the following sections I will describe the various tumour types and examine to what degree these predictions hold true. We will see that although we have so far treated skin cancer as a homogeneous entity, in term of causation, we will have to refine our ideas a little.

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