Understanding Pharmacogenomics

Approved by the Cancer.Net Editorial Board, 01/2020

Pharmacogenomics studies how medicine interacts with inherited genes. This includes how inherited genes affect the way medications work for each person. Genetic differences mean that a drug can be safe for one person but harmful for another. One person may experience severe side effects from it. Another may not, even when given a similar dose.

How pharmacogenomics differs from genetic testing

Standard genetic testing is a type of testing that searches for specific genes. For example, a test may look for BRCA1 and BRCA2 genes, which are linked with a higher risk of breast and ovarian cancer. The results from standard genetic test may prompt preventive or risk reduction steps. These include:

  • More frequent cancer screening

  • Lifestyle changes

  • Preventive treatment

Pharmacogenomics is a type of genetic testing. It looks for small variations within genes. These variations may affect whether genes activate or deactivate specific drugs. Test results help the doctor choose the safest and most effective drug and dose.

Pharmacogenomics is constantly changing. Researchers continue to identify gene variations that affect how a drug works. As personalized medicine grows, testing for gene variations may become more common.

Why drugs work differently in different people

Drug activation. Many drugs that treat cancer need to be "turned on" to work. This process is called activation. Proteins called enzymes speed up chemical reactions in the body. This activates a drug so that it can do its job.

Each person inherits variations in enzymes. The variations affect how fast a drug changes into its active form. For example, some bodies break down drugs slowly. This means standard doses of treatment may not work as well.

Drug deactivation. Drugs also need to be "turned off" to limit the drug’s exposure to healthy tissues. This process is called deactivation.

Some people may have slower enzymes. As a result, high levels of the drug may remain in their bodies for a long time. This means that they may have more side effects from the drug.

Besides pharmacogenomics, other factors may influence a person’s reaction to a drug:

  • Age and gender

  • The cancer’s stage

  • Lifestyle habits, such as smoking and drinking alcohol

  • Other diseases

  • Medications taken for other conditions

Benefits of pharmacogenomics

Here are some of the benefits of pharmacogenomics:

It may improve patient safety. Severe drug reactions cause more than an estimated 120,000 hospitalizations each year. Pharmacogenomics may prevent these by identifying patients at risk.

It may improve health care costs and efficiency. Pharmacogenomics may help find appropriate medications and doses more quickly.

Challenges to pharmacogenomics

Here are some challenges in the development and practical use of pharmacogenomics:

  • It is expensive, particularly if insurance does not cover the costs.

  • Access to certain tests may be limited in some places.

  • Privacy issues remain, despite federal anti-discrimination laws. These laws prohibit discrimination based on genetic information.

Pharmacogenomic testing in practice

Here are some examples of pharmacogenomic testing in cancer care:

Colorectal cancer. Irinotecan (Camptosar) is a type of chemotherapy. Doctors commonly use it to treat colon cancer. In some people, genetic variations cause a shortage of the UGT1A1 enzyme. This enzyme is responsible for metabolizing irinotecan. Metabolism is the chemical reaction that helps the body process the drug.

With a UGT1A1 shortage, higher levels of irinotecan remain in the body. This may lead to severe and potentially life-threatening side effects. The risk is greater with higher doses of the drug.

Doctors may use a pharmacogenomic test called the UGT1A1 test. It shows which people have this genetic variation. Then, the doctor may prescribe a lower dose of irinotecan. Often, the lower dose is just as effective for these people.

Acute lymphoblastic leukemia (ALL). Doctors use pharmacogenomic testing for children with ALL. About 10% of people have genetic variations in an enzyme called thiopurine methyltransferase (TPMT). TPMT is responsible for metabolizing chemotherapy for ALL.

Children with lower TPMT levels receive lower chemotherapy doses. This helps prevent severe side effects.

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 lower levels of the enzyme called dihydropyrimidine dehydrogenase (DPD). DPD helps the body metabolize fluorouracil.

Doctors may use a pharmacogenomic test to find this variation. If found, a lower fluorouracil dose helps prevent serious side effects.

Questions to ask the health care team

Talk with your health care team about your treatment options and consider asking the questions below:

  • What are my cancer treatment options?

  • Which treatment or combination of treatments do you recommend? Why?

  • Do these treatments work differently in different people? If so, are there tests to find these differences?

  • What are the possible side effects of this treatment?

  • Could my genetic makeup affect my body’s response to treatment?

  • Is there a way to predict how my body will respond to this drug? Or to predict whether I might experience severe side effects?

  • Whom should I call with questions or problems?

Related Resources

The Genetics of Cancer

More Information

National Institutes of Health: Pharmacogenomics FAQ