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Gene analysis might explain ethnic differences in sensitivity to chemotherapy in lung cancer

DALLAS April 23, 2007 -- Analysis of three genetic mechanisms that cause non-small cell lung cancer might explain why East Asians respond better than other ethnic groups to a certain type of chemotherapy, a team led by UT Southwestern Medical Center researchers has found.

This type of analysis might become useful in tailoring cancer treatments to individual patients, the researchers said.

"Genetic differences may help explain why so many Asian women who never smoked develop lung cancer," said Dr. Adi Gazdar, professor of pathology at UT Southwestern and senior author of a study appearing online today in Public Library of Science Medicine.

The researchers focused on a protein called the epidermal growth factor receptor, or EGFR, which lies on a cells surface and is involved in controlling many processes. Excessive amounts of EGFR are known to be involved in several types of cancer, including more than half of lung cancers. Several drugs that interfere with EGFR are used as chemotherapeutic agents.

Three inherited alterations, known as polymorphisms, in the gene that codes for EGFR can cause cells to make abnormally high levels of the protein, Dr. Gazdar said. One polymorphism shortens a portion of the gene, while two other abnormalities involve variations in the genetic "alphabet," or sequences of chemical building blocks that make up the gene.

Increased levels of EGFR also can be caused by spontaneous mutations in the gene, or by an effect in tumor cells that increases the number of copies of genes coding for EGFR.

In the current study, the researchers compared the genes of 250 healthy people of various ethnicities with 556 samples of benign and cancerous lung tumors. They found that the three inherited polymorphisms were less common in healthy people from Japan and Taiwan than in healthy people of European, African or Mexican descent.

This suggests that this population normally ma
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
23-Apr-2007


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