Study Identifies Genes That Predict Painful Chemotherapy Side Effects

Study Identifies Genes That Predict Painful Chemotherapy Side Effects

Chemotherapy-induced peripheral neuropathy is not only painful – it’s hard to predict — affecting up to 40 percent of cancer patients who undergo treatment. But now researchers at the Mayo Clinic say they have discovered gene variations that could someday help doctors identify which patients are more susceptible to the often debilitating condition.

In what’s being described as the first of its kind study to explore such a large swath of the human genome, three genes have been singled out as predictors of chemotherapy side effects. It’s a discovery that may enable physicians to improve cancer treatment by individualizing a patient’s care to their risk for a particular chemotherapy side effect.

bigstock-Genetic-Code-3335806“Our study creates a path for how to approach the whole genome in order to tailor cancer treatments,” said Andreas Beutler, MD, an oncologist at Mayo Clinic Cancer Center and senior author of the study. “That is important because we not only want to cure people’s cancer or help them live longer, but we also want to provide them with the best quality of life.”

Symptoms from chemotherapy-induced peripheral neuropathy can be as mild as a tingling or numbness. But over time, they can progress to a loss of feeling in the hands and feet — to the point where patients can no longer walk normally and are left with a permanent feeling of numbness or pain.

Currently, there is no way to predict which patients undergoing chemotherapy will develop neuropathy or to what degree. There are few effective treatments and the chronic pain is often so debilitating that cancer patients stop their chemotherapy early.

Approximately 50 genes are linked to a hereditary form of peripheral neuropathy. Many patients who have one of these genes experience no symptoms until they are exposed to chemotherapy. After first considering those genes as the most likely suspects, Dr. Beutler expanded his search to the wider human genome for other predictors.

Researchers studied more than 20,000 genes from 119 cancer patients, over half of whom had developed chemotherapy-induced peripheral neuropathy during the course of a clinical trial.

One gene from the initial 50 emerged that appeared to predispose patients to chemotherapy-induced peripheral neuropathy. Two others were discovered after researchers analyzed the remaining 20,000 genes.

The results suggest that hereditary neuropathy and chemotherapy-induced peripheral neuropathy may share genetic roots in some patients.

Dr. Beutler and his team plan to expand their study to look at the entire human genome in as many as 1,000 cancer patients.

“What we are doing is much larger than just uncovering a handful of genes. We are using cutting-edge genomics research to enhance our strengths in clinical trials and develop new methods to individualize medicine,” Beutler said.

This latest discovery follows a study released by researchers at the University of Michigan that found the anti-depressant drug duloxetine (Cymbalta) shows great promise in lessening the neuropathic pain of patients who undergo chemotherapy.

Authored by: Richard Lenti