7. Pharmacogenomics, pharmacogenetics and cancer

7.2. Germline variation

Knowledge about inherited DNA variation in the patient’s healthy tissue (as opposed to new mutations arising within a tumour) can:

  • Help select the right treatment for the patient.
  • Help with decisions about dosing.
  • Predict the likelihood of adverse reactions from treatment.

For example, genetic variation can affect how a patient’s body breaks down (metabolises) a medicine. This can affect how well the medicine works. ‘Tamoxifen’ is a treatment for breast cancers that are known as ‘hormone-receptor positive’. Tamoxifen is converted in the body by the enzyme CYP2D6 into several molecules that target the tumour, including ‘endoxifen’. Some patients have a genetic variation that means they have low CYP2D6 enzyme activity, and therefore they produce less endoxifen. Levels of CYP2D6 have been linked to how well patients respond to tamoxifen. Other studies suggest that if the dose of tamoxifen is increased, it can help these patients and lead to higher levels of endoxifen in their blood.

Many treatments for chronic diseases may lead to side effects and some of these may be severe or serious. Research into how to use genetics to predict such severe adverse reactions is progressing. For example, recent research shows that the following can be predicted based on genetic information:

  • The risk of heart muscle damage from ‘anthracycline’ chemotherapy.
  • The risk of hearing damage from the medicine ‘cisplatin’.