Can Race Affect How Drugs Work?

Your genes can effect how you respond to medications.

People can differ in their response to medications based on their genetic makeup, and sometimes the genes at work are clustered in specific races and ethnicities. Recently, for instance, scientists discovered why some leukemia patients having a Chinese, Japanese or Korean background tend to be extremely sensitive to the cancer drug, mercaptopurine.

Pharmacogenetics and Pharmacogenomics

The study of the interaction between genetics and therapeutic drugs is called pharmacogenetics or pharmacogenomics.

The difference between the two has to do with the initial approach of the science:

  • Pharmacogenetics starts with an unexpected drug response and looks for a genetic cause.
  • Pharmacogenomics starts by looking for genetic differences within a population that might explain special responses to a drug or special susceptibility to a health problem.

If these two definitions sound alike to you, you are not alone. Many scientists use the terms interchangeably. For the remainder of this article, the interest in pharmacogenetics relates mainly to a recent finding in the treatment of leukemia.

Genetic Basis of Drug Toxicity

Scientists at St. Jude Children's Research Hospital just published their findings in the Journal of Clinical Oncology. It turns out that about 10 percent of young leukemia patients who have an East Asian (Chinese, Japanese and Korean) background inherit a gene type that is associated with difficulty tolerating a drug that is considered indispensable for curing acute lymphoblastic leukemia (ALL), the most common childhood cancer.

Genes and Mercaptopurine for ALL

Researchers discovered that individuals who inherited a variation in the NUDT15 gene were extremely sensitive to the drug mercaptopurine. Patients with the genetic variant needed to have their dose of mercaptopurine reduced as much as 92 percent, for standard doses, were associated with side effects and treatment delays that would jeopardize treatment success.

At St. Jude, 94 percent of newly diagnosed ALL patients now become long-term survivors.

Not only East Asians, but also Hispanics were more likely to inherit the gene variant than those from other racial and ethnic groups, according to the study. Nearly 10 percent of the East Asian group had the gene variant, compared to about 4 percent of Hispanics. The variant does occur in people of European and African ancestry, but much more rarely.

Another gene, TPMT, had also been implicated in reduced mercaptopurine tolerance, and had also been linked to mercaptopurine toxicity in Korean patients with inflammatory bowel disease. (Mercaptopurine, 6-MP, is also used for inflammatory disease of the bowel, such as in preventing Crohn’s disease recurrence).

St. Jude’s had already begun routinely testing for the TPMT variants; the results help determine the mercaptopurine dose patients receive. But the more recent discovery of NUDT15 variants helps to flesh out the understanding of inherited genetic risk factors, said investigators.

Nonetheless, investigators noted, genetic and non-genetic factors remain to be discovered to improve the safety and effectiveness of mercaptopurine treatment for children with ALL.

The signs and symptoms of leukemia and other blood cancers can be hard for general practitioners to spot at first, and may be the same as many other less serious conditions.

More on Acute Lymphocytic Leukemia

Acute lymphocytic leukemia is a type of leukemia that mostly affects children. ALL can also affect adults, but at a lower rate. It can also be referred to as acute lymphoblastic or acute lymphoid leukemia. For more on ALL and it’s diagnosis see the article on the diagnosis of Leukemia by an oncology nurse, Karen Raymaakers.

Sources

Pharmacogenetics/Pharmacogenomics. http://www.genetics.edu.au/Publications-and-Resources/Genetics-Fact-Sheets/FactSheet25. Accessed February 2015.

Study identifies genetic basis of drug toxicity in leukemia patients of East Asian ancestry. http://www.news-medical.net/news/20150202/Study-identifies-genetic-basis-of-drug-toxicity-in-leukemia-patients-of-East-Asian-ancestry.aspx. Accessed February 2015. 

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