Understanding Pharmacogenomics

Approved by the Cancer.Net Editorial Board, 06/2015

Pharmacogenomics is the study of how our inherited genes affect the way our bodies process and respond to drugs. It is also called pharmacogenetics. Genetic differences in people mean that a drug can be safe for one person but harmful for another person. For instance, some people experience severe side effects from a drug, while others may not, even when given a similar dose.

How pharmacogenomics differs from genetic testing

In standard genetic testing, people are tested for the presence of entire genes. For example, testing for the breast cancer genes BRCA1 and BRCA2 can tell you if you have a higher risk of breast and ovarian cancers. The results of these genetic tests may prompt some people to have additional cancer screenings, make lifestyle changes to avoid other risk factors, and choose preventive treatment.

Pharmacogenomics is a specific kind of genetic testing. This testing looks for small variations within genes to help identify differences in a person’s ability to activate and deactivate drugs. The results of these tests can help the doctor choose the safest and most effective dose of a drug.

Pharmacogenomics is constantly changing. As personalized medicine becomes more common for cancer care, testing for gene variations may also become more common. Researchers continue to identify additional gene variations that affect a person’s response to a drug. This, in turn, better enables doctors to match patients with specific treatments.

Why drugs work differently in different people

Many drugs that treat cancer are not fully active in the form in which they are given. Instead, drugs need to be activated (“turned on”) by special proteins that speed up chemical reactions in the body. These are called enzymes. Each person inherits variations in these enzymes that affect how fast or efficiently these drugs are changed to their active form. Some people break down drugs slowly. This means that the standard doses of treatment may not work as well.

Drugs also need to be deactivated (“turned off”) to limit the drug’s exposure to healthy tissues. A person with less efficient or slower enzymes may have high levels of the drug remain in the body for a long time. This means that the person may have more side effects from the drug.

Besides pharmacogenomics, other factors may influence how a person reacts to a drug. These include:

  • A person’s age and gender
  • How advanced the cancer is
  • A person’s lifestyle habits, such as smoking and drinking alcohol
  • Other diseases that a person has and the medications a person takes for these conditions

Benefits of pharmacogenomics

Pharmacogenomics offers important benefits:

Improves patient safety. It is estimated that severe drug reactions cause more than 120,000 hospitalizations each year. Pharmacogenetic testing may help identify patients who are likely to experience dangerous reactions to drugs beforehand.

Improving health care costs and efficiency. The time and resources that doctors and patients spend finding appropriate medications and doses through “trial and error” is likely to fall as pharmacogenomic tests are developed.

Challenges to pharmacogenomics

Meanwhile, there are some challenges in the development and practical use of pharmacogenomics.

  • It can be expensive, especially if insurance companies don’t cover the test costs.
  • Not all tests may be widely available.
  • There could be privacy issues, even though federal laws make it illegal for companies and insurers to discriminate against people based on their genetic information.
  • There may be other, unresolved ethical and legal issues.

Pharmacogenomic testing in practice

Here are some examples of pharmacogenomics testing in cancer care:

Colorectal cancer. Irinotecan (Camptosar) is a type of chemotherapy commonly used to treat colon cancer. In some people, genetic variations cause a shortage of the UGT1A1 enzyme. This enzyme is responsible for the body’s metabolism, or breakdown, of irinotecan. In these people, higher levels of irinotecan remain in their body. This may lead to severe and potentially life-threatening side effects, especially if higher doses of the drug are used.

Doctors may use a pharmacogenomic test called the UGT1A1 test to see which patients have this genetic variation. If a person does have this genetic difference, the doctor can prescribe a lower dose of irinotecan. Often the lower dose is just as effective for these people.

Acute lymphoblastic leukemia (ALL). Doctors also use pharmacogenomic testing for children with acute lymphoblastic leukemia. Genetic variations in an enzyme called thiopurine methyltransferase (TPMT) are found in about 10% of children. TPMT is responsible for the metabolism of chemotherapy that is used to treat ALL. To avoid severe side effects, children with lower levels of TPMT are treated with lower doses of these drugs.

Other cancer types. Fluorouracil (5-FU) is a type of chemotherapy. It is used to treat several types of cancer, including colorectal, breast, stomach, and pancreatic cancers. A genetic variation in some people causes them to have lower levels of the enzyme called dihydropyrimidine dehydrogenase (DPD), which helps the body metabolize fluorouracil. Doctors may use a pharmacogenomic test to find this variation in patients. This allows them to lower the dose of the drug to avoid serious side effects in these patients.

Questions to ask the doctor

Talk with your doctor to find out more about how your genetic makeup may affect your body’s response to a specific drug when discussing your treatment options. Consider asking the following questions:

  • Would you explain my treatment options?
  • Which treatment or combination of treatments do you recommend? Why?
  • What are the possible side effects of this treatment?
  • Is there a way to predict how my cancer will respond to this drug or whether I might experience severe side effects?
  • What are my options if the cancer does not respond to the drug or if I suffer from severe side effects?
  • Whom do I call for questions or problems?

More Information

Facts About Personalized Cancer Medicine

Explaining Cancer Genome Research

Additional Resource

American Medical Association: Pharmacogenomics