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New York Team Links Mutation to Mortality in Lung Cancer Patients

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Patients with an early form of non-small-cell lung cancer are “more than twice as likely” to die of the disease within four years if they have a mutation in the p53 oncogene, according to research conducted at the University of Rochester, in New York.

Traditionally, patients with early-stage lung cancer receive surgery but not chemotherapy or radiation treatment unless the cancer recurs. If scientists know that certain patients are much more likely to die of the disease — such as patients with mutations in the p53 gene — physicians may consider preventive chemotherapy earlier in their treatment regimens.

Steven Ahrendt, a researcher at the school’s James P. Wilmot Cancer Center, analyzed tumors from 188 patients with the cancer and found that the status of the p53 gene plays a pivotal role in distinguishing which patients are most likely to survive four years or more.

Ahrendt’s prospective study identified a sub-group of patients in whom cancer was diagnosed early and who do not have a p53 mutation. His team found that 78 percent of these patients lived four years or more — a survival rate four times higher than for similar patients.

The researchers found mutations of the p53 gene, which normally produces a protein that helps repair or destroy damaged DNA, in 55 percent of the 188 tumors. In their study, 48 percent of early-stage lung cancer patients with a p53 mutation died within four years, compared to 22 percent of patients without the mutation.

The team also found that the type of p53 mutation matters: Patients with mutations that substituted one base for another “fared better” than patients with mutations that knocked out the function of the tumor-suppressing protein made by the gene. Results of their study appear in the July 2 issue of the Journal of the National Cancer Institute.

Lung cancer is the leading cause of death by cancer in men and women, and fewer than one in five patients live five years after diagnosis. However, between 40 percent and 60 percent of people in whom the disease is caught in the earliest stages live beyond five years.

“We need to confirm these results through a larger study, but this difference is large enough to be clinically meaningful,” said Ahrendt, who is also associate professor of surgery, oncology, and pathology at the university.

According to the researcher, “there is no easy, inexpensive blood test to check [a patient’s] p53 status.” The molecule is a “popular pharmaceutical target for drugs in development because it’s involved in many types of ... tumors, including breast, ovarian, bladder, brain and prostate cancers,” Ahrendt said.

— KL

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