Genetic differences explain severity of chemotherapy side effects

Tuesday, June 8th 2004, 1:20 pm

By: News On 6

NEW ORLEANS (AP) _ Genetic differences among cancer patients may help explain why some become terribly sick during their treatment and others find chemotherapy a relative breeze.

The genetic defects that trigger cancer vary from person to person. Individualizing treatment to target the genetic signals driving each patient's tumor is an often-discussed goal, though still not routinely achieved.

Less attention has been paid to the genetic differences in the rest of the body that influence how miserable patients become while going through cancer therapy. Reports at the annual meeting in New Orleans of the American Society of Clinical Oncology, which concluded Tuesday, described the beginning attempts to sort this out.

Understanding individual genetic differences ``may explain why one person will benefit from a drug and another will not or why someone has severe toxicity,'' said Dr. Harry Bleiberg of the Jules Bordet Institute in Brussels.

For now, this research is unlikely to have much effect on how patients are treated. But someday, it may be possible to tailor treatments to patients' side effects as well as their likelihood of being cured.

``It is really important. This could dictate the size of the dose we give or maybe whether we don't give a drug at all,'' said the oncology organization's president, Dr. Margaret Tempero of the University of California at San Francisco.

In one study involving 494 patients, Dr. Jeff Sloan and others from the Mayo Clinic looked for differences in genes that regulate the body's use of the vitamin folate. He found these genetic patterns seem to influence how well patients do on a three-drug combination for advanced colon cancer. Possible side effects from the treatment include fatigue, diarrhea, nausea, vomiting, dehydration, low white-cell counts and numbness of the hands and feet.

Many normal genes are found in slightly variant forms. The Mayo team looked at a gene called DPYD and found that people with two variations were significantly less likely than those with the usual form to suffer fatigue.

In addition, those with a bit of genetic code called TSER near another folate gene known as TYMS were more likely to report a positive outlook while on chemotherapy.

``We believe we have found evidence of a relationship between the genetic makeup of cancer patients and their quality of life, even before treatment begins,'' Sloan said.

Another study, conducted by Dr. Rebecca Suk of Massachusetts General Hospital, identified a genetic variation that seems to influence whether people treated for advanced non-small cell lung cancer experience vomiting and other severe gastrointestinal side effects while on chemotherapy.

Her team looked for variations in a gene involved in DNA repair in 147 patients. They found that 30 percent of those with unusual forms of this gene were likely to have particularly bad side effects, compared with just 14 percent who had the standard gene.

The researchers speculate that people with the variant form of this gene, called ERCC1, do a worse job of repairing damage caused by the chemotherapy, and this explains their severe side effects.

``A lot more studies need to be done before we can apply this in the clinic,'' Suk said. ``But it may be possible to identify people who are at high risk and use that to choose their therapy.''