Each cancer patients response to chemotherapy is unique. Some may experience nausea and immune deficiency, while others can experience a more severe adverse condition known as chemotherapy-induced peripheral neuropathy (CIPN) a form of nerve damage that can be so debilitating, it often prompts patients to stop treatment early.

Doctors have had a hard time predicting which patients will ultimately develop CIPN, making it difficult to tailor treatment so that it is most effective for each individual. But now, new research has revealed seemingly benign genetic mutations that may influence who develops this painful side effect.

In a study from the Mayo Clinic Cancer Center, researchers have implicated the genes EPHA5, ARHGEF10 and PRX as playing significant roles in the development of CIPN. This discovery can ultimately help doctors to have a better understanding of CIPN and whether or not their patients should move forward with certain cancer treatments.

Chemotherapy-induced peripheral neuropathy is one of the most important, unmitigated side effects of chemotherapy, lead author Dr. Andreas Beutler, an oncologist at the Mayo Clinic Cancer Center, told FoxNews.com. You have some other side effects that used to be very important such as nausea and immune deficiency but special medications have been developed. With CIPN, it has actually become the most prominent and troubling side effect for many chemotherapy patients, because there is no medication for it.

Peripheral neuropathy is caused by damage to the peripheral nerves, which are furthest away from the brain and spinal cord. When chemotherapy damages these nerves, the condition becomes CIPN. Symptoms vary in type and intensity depending on which peripheral nerves are damaged, but they typically include shooting pain, burning, tingling or electric shock-like pain, loss of feeling, balance issues and muscle weakness. The symptoms can become so severe that patients lose the ability to walk normally and are left with permanent numbness in their extremities.

CIPN affects an estimated 30 to 40 percent of patients, but there is no current way to determine who will experience it or how severe it will be.

Beutler and his colleagues decided to analyze the genetics of cancer patients through exome sequencing - a form of DNA analysis that selectively sequences the parts of the genome responsible for coding functional proteins. Known as the exonic region, this area is estimated to house 85 percent of all disease-causing genetic mutations.

The researchers performed exome sequencing on 20,794 genes from 119 cancer patients. Half of the patients were experiencing CIPN during their chemotherapy trial.

The genome is three billion nucleotides, meaning the whole genome has three billion different positions, Beutler said. Out of those, we assessed 60 million of each patient that are best understood the exome. Thereby, we could get a very good view of the part of the genome that is most important and most relevant to our question.

Exome sequencing of the more than 20,000 genes lead the researchers to EPHA5 a previously implicated gene in hereditary peripheral neuropathy as well as two new genes ARHGEF10 and PRX. Genetic mutation in all three areas was associated with a predisposition to CIPN.

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Genetic mutations may predict who will develop chemotherapy side effects

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