Gene could matter in bladder cancer

A variant form of the iNOS gene seems to increase survival among people with the malignancy

DENVER — Among people with the most common form of bladder cancer, patients harboring a variant of a certain gene survive twice as long as those who have the more common version of the gene, researchers reported April 20 at a meeting of the American Association for Cancer Research.

The researchers found the gene association by screening blood samples from 596 people with superficial, or non-invasive, bladder cancer for variants in 35 inflammation-related genes. The analysis showed that patients with the common form of one these genes, called iNOS, had an average survival without a cancer recurrence of less than four years. Patients with a variant form of iNOS survived without recurrence for eight years on average. The iNOS gene encodes a protein called inducible nitric oxide synthase. This compound synthesizes nitric oxide, a key compound in all mammals that facilitates cell-to-cell signaling and also plays a role in inflammation.

Inflammatory genes were studied because BCG, a standard bladder cancer treatment that reduces cancer recurrence, “may function through modulation of the inflammation pathways of the human immune system,” says study coauthor Hushan Yang, an epidemiologist at the University of Texas M.D. Anderson Cancer Center in Houston. BCG is shorthand for bacille Calmette-Guérin.

The extended survival and lower recurrence rate with the variant form of the iNOS gene occurred only in patients getting BCG, which is injected intravenously.

Yang says it remains unclear exactly how the variant form of iNOS imparts an anticancer advantage in patients getting BCG.

Many research groups are pursuing this line of study, with the goal of  creating a patient DNA profile that is relevant to the cancer that person is fighting, says John Witte, a genetic epidemiologist at the University of California, San Francisco. “It’s clear that people do differently based on their genetics,” he says. The DNA profile using iNOS “could have near-term clinical impact, if it is shown to be causal.”

But it’s still too early to know when this and other similar approaches will be ready for the clinic, he says. “It could be a year from now or five years,” he says. “But I know in our lifetimes it is going to happen.”

Up to 70 percent of bladder cancers are superficial cancers — cases in which the patients are unlikely to have their bladder removed. But despite options including tumor surgery, chemotherapy and BCG, these patients still have a 70 percent chance of relapse over five years, even after initially successful treatment, Yang says.

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