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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