Chemotherapy Resistance Varies with Ethnicity

Chemotherapy Resistance Found To Vary With Ethnicity

A genetic mutation affecting resistance to chemotherapy occurs more frequently in some ethnic groups than in others according to a new study.

Researchers found that African and African American populations included more individuals with the drug-resistant gene than Caucasian or Asian populations. This might help explain why some people of African descent respond poorly to chemotherapy. The research was presented March 25 at the annual meeting of the American Association for Cancer Research in New Orleans.

"We now know that the genetic influence on drug resistance is not the same throughout the whole population," says Howard L. McLeod, Pharm.D., associate professor of medicine, of pharmacology and molecular biology and of genetics at Washington University School of Medicine in St. Louis. "Because of this work, we can try to solve the problem."

Dr. McLeod, who led the international team of researchers from his previous position at the University of Aberdeen in the United Kingdom, specializes in pharmacogenetics, an emerging research field. Margaret-Mary Ameyaw, M.D., Ph.D., of the University of Aberdeen is the study's first author and will join the Washington University faculty later this year.

The mutation studied by Dr. McLeod and his colleagues changes production of a protein called P-glycoprotein, or PGP, a molecular pump that rids cells of drugs. When working correctly, PGP pumps chemotherapeutic drugs out of tumors, allowing the tumor cells to survive. This response is known as drug resistance. The genetic mutation means the PGP pump stops working, allowing drugs to enter and kill tumor cells.

PGP also rids cells of many other medications, such as HIV protease inhibitors and drugs used to control high blood pressure and prevent failure of kidney transplants.

Working with collaborators in five countries, Dr. McLeod and his colleagues did DNA tests on blood samples from 1,280 people from 10 ethnic populations. The researchers studied Ghanaian, African American, southwest Asian, British Caucasian and Saudi populations as well as people native to Portugal, China, Kenya, the Sudan and the Philippines.

They found that some populations were significantly more likely than others to contain the mutation.

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