Memphis researchers have found further evidence that normal genetic variations impact how the body responds to medications, but don't expect a DNA test before a doctor writes your next prescription.

The St. Jude Children's Research Hospital study of 240 young leukemia patients linked certain normal biochemical variations in four genes with a dramatically increased risk of medication side effects such as liver problems, mouth ulcers, infections, diarrhea, foot or leg numbness and pain.

In one example, patients with one gene variation were 17 times more likely than patients with a different version of the same gene to suffer liver problems that might delay treatment and reduce the odds for a cure. Another variation was associated with a 10-fold higher risk of developing mouth ulcers.

Writing in a recent issue of the scientific journal "Blood," the investigators reported their latest results reinforce the hope that genetic screening will lead to more tailored therapies by better predicting which patients will likely benefit from a given medicine at a given dose and which would likely suffer dangerous side effects. The technology already is used at St. Jude to help determine how much of a key anti-leukemia drug patients receive.

In the roughly four years since the human genetic code was deciphered, efforts to replace the trial-and-error approach to prescribing drugs with one based on a patient's DNA have generated plenty of excitement and a handful of practical applications.

That's because the dream of genetically based, individualized prescribing is starting to confront biological and commercial realities, Dr. Mary Relling explained. She is senior author of the report and chair's the St. Jude pharmaceutical sciences department.

"I think we oversold individualized medicine," she said. "It will help in some situations. It is already having a bit of an affect. But we have to be aware of the possibility that biology might be complicated."

Others are more upbeat about the prospects for the field, known as pharmacogenetics.

National Institutes of Health anticipates spending more than $150 million by 2010 on projects ranging from how genes influence a person's response to blood pressure and asthma medications to identifying the inherited gene variations that help explain why some patients benefit from drugs used to treat irregular heart beats, while others are harmed. St. Jude is one of 12 U.S. centers that is part of the NIH's Pharmacogenetics Research Network.

Last fall, Sen. Barack Obama (D-Ill.) introduced the first legislation designed to spur development through funding, cooperation and a regulatory overhaul. The measure includes proposed tax credits for private research aimed at moving screening from the laboratory and to the clinic faster.

This spring the nation's largest pharmacy benefits management company launched a study into whether screening for certain genetic variations could help doctors better manage patients starting the blood-thinner Warfarin. The study is designed to evaluate the medical, clinical and cost-saving potential of such testing. It is a collaboration between Medco Health Solutions and the Mayo Clinic. Results are expected later this year.

Dr. Howard McLeod said a genetic screening test is also available to identify breast cancer patients who are less likely to benefit from the medicine drug Tamoxifen and, thus, need to consider other drugs. McLeod directs the University of North Carolina, Chapel Hill, Institute of Pharmacogenomics and Individualized Therapy.

While it will likely be some time before genetic testing plays a role in most medication decisions, McLeod said it is already proving useful for select patients, including those taking certain medicines drugs that have rare but devastating side effects.

"Not all drugs need individualized therapy," he said, but everyone already knows someone who would benefit from genetic-guided therapy.

St. Jude's been using pharmacogenetics for more than 13 years to determine a safe dose of the anti-leukemia medicine drug Mercaptopurine.

St. Jude investigators have expanded their search for important gene variations from the 16 included in this study to 600,000 bits of genetic material. That's still just a fraction of the estimated 10 million pieces of DNA that vary from person to person. Results are expected next year.

The genetic variety between individuals is daunting. Relling said it will likely make linking a particular medication drug response to certain gene variations difficult.

Even if such links are found, she said it isn't clear if the pharmaceutical industry would respond with different formulas of a medicine to match the needs of each new sub-group of patients. "There is no way to force anyone to make a drug," she said.

-- Mary Powers: 529-2383