Genetic testing, the present and future of chemotherapy

Based on “Combien de morts ça va prendre?” by Marie Claude Malboeuf, La Presse

At 69 years old, Paul Allard had just gotten a colon tumor removed, had no traces of metastasis and was given a 3 in 4 chance of being cancer-free for the rest of his life. He opted to undergo oral chemotherapy to further decrease his risk of recurrence and took capecitabine tablets. Two weeks later Paul Allard was agonizing in the ICU and died within a few days of admittance.

Capecitabine and DPD deficiency

Capecitabine is a pro-drug, which is converted to 5-fluorouracil (5-FU) by enzymes in the body. While 5-FU has long been used to fight cancer, it causes the death of 0.5% to 1.3% of users and leads to the hospitalization of 15% of users due to side effects. Most people are able to clear 5-FU from their bodies, but some have a mutation in their DPYD gene, which is responsible for the production of the enzyme dihydropyrimidine dehydrogenase (DPD) that breaks down 5-FU. This mutation results in a DPD deficiency and very high levels of 5-FU, as the body is unable to clear it efficiently. This high level of toxicity causes more severe side effects than usual and can lead to death, as was the case for Paul Allard. Although it is rare to have a complete DPD deficiency, it is believed that 3% to 6% of people have a partial DPD deficiency.

How does genetic testing help?

In patients with DPD deficiency, the use of 5-FU is highly discouraged, as it is not safe. However, no one had warned Paul Allard or his wife about these risks, let alone inform them of genetic tests that could have saved his life. While there have been a number of stories similar to Paul Allard’s, there have been some improvements in the administration of chemotherapy. Genetic testing to determine a patient’s drug response prior to chemotherapy is becoming more common. In France, genetic testing is performed in cancer patients by over 80 hospitals in order to identify genetic mutations that could be problematic for cancer treatments. These tests allow for the personalization of the patients’ treatments and decrease the risk of toxicity. They also help avoid hospitalizations due to a “trial-and-error” method of treatment and minimize patients’ suffering. Such genetic tests are not yet mandatory in Canadian hospitals, but they may soon be offered in Quebec.

Currently, GeneYouIn is the only drug response service provider in Canada that includes the DPYD and TPMT genes. Visit us at to learn how genetic testing can help you or a loved one. Subscribe to our newsletter to receive updates and news on the genetics of drug response and follow us on Facebook and Twitter for the latest pharmacogenetics news.

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