Gene May Accelerate Cancer Drug Metabolism, Leading To Poor Outcomes

A new study published in the journal, Cancer Research, may have identified a genetic explanation for why some cancer patients have poorer outcomes after treatment. The researchers found that some patients with breast cancer, lung cancer or leukemia, expressed a gene that caused them to metabolize oncology drugs more quickly.

CYP3A7 is a gene that is usually only expressed in infancy, however some people continue to express the gene product into adulthood, leading to an accelerated metabolism. The enzyme produced by the CYP3A7 gene is responsible for breaking down hormones, but it can also catabolize a number of pharmaceuticals, potential reducing the effectiveness of anti-cancer compounds.

Researchers at The Institute of Cancer Research in London, identified that between seven and eight percent of the 2,500 patients studied, had a number of point mutations in the DNA sequence for CYP3A7. The study investigators believe that these variations are responsible for allowing the gene to be active in adults.

This cluster of genetic mutations has previously been linked to an increased risk of developing breast cancer. The researchers studied samples taken from 1,128 patients with chronic lymphoid leukemia, 1,008 women with breast cancer and 347 patients with lung cancer, to identify this correlation between the gene variant and poor outcomes.

“Our study shows that some patients with breast cancer, lung cancer and leukemia carry a genetic variant which increases their capacity for breaking down hormones – and potentially drugs,” said Dr. Olivia Fletcher, Group Leader in the Breast Cancer Now Research Centre at The Institute of Cancer Research, and a lead author on the study. “We showed that patients with the variant tend to have worse outcomes than those without, and one possibility is that they are eliminating chemotherapy drugs from the body too efficiently.”

According to the researchers, the patients with the genetic mutations had poorer prognoses after treatment. Breast cancer patients faced a 74 percent higher risk of dying of the disease, while lung cancer patients had a 43 percent increased risk of death from any cause. Among leukemia patients, the variant was associated with a 62 percent higher risk of further progression of the disease.

The results of this study suggest that cancer patients with the CYP3A7 variant could benefit from different treatment options, compared to those without the mutations. “We will need further studies to determine whether the genetic variant is exercising its effect by interfering with treatment, and if so, exactly how it is affecting treatment,” said Fletcher. “Our research won’t have an immediate impact on clinical practice, but in the longer term, doctors might be able to take into account the presence of this – and other – genetic variants in planning treatment, in order to make sure that all patients have the treatment that is best for them.”