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Evolutionary principles used to predict cancer
March 29,
2006
Courtesy The Wistar Institute
and World Science staff
In diverse ecosystems, packed with wildly different species, evolution moves quickly, researchers say. This phenomenon, they add, happens in ecosystems ranging from marine sediments to mountain forests and—as a new study has found—precancerous tumors.
Cancer occurs when cells accumulate enough genetic changes to become malignant, which causes them to reproduce out of control. This progression of changes is a sort of evolution of cells, scientists believe.
In a study published online March 26 in the research journal Nature
Genetics, Carlo Maley of New York’s Wistar Institute and colleagues reported that precancerous tumors containing highly diverse cells are more likely to evolve into cancer than those containing genetically similar cells.
The finding suggests that, in at least some forms of cancer, the more genetically diverse a precancerous tumor is, the more likely it is to progress to cancer, the researchers added. Thus, genetic diversity might act as a red flag for cancer risk in patients with precancerous tissues.
“Although researchers first defined cancer in evolutionary terms in the 1970s, few researchers have actually studied the disease this way,” said Maley, lead author of the study. “We wanted to know: If we measured a precancerous tumor’s genetic diversity at baseline, could we predict who would go on to get cancer?”
The scientists analyzed data on a precancerous condition called Barrett’s esophagus. In this condition, cells lining the lower esophagus change due to repeated exposure to stomach acid from reflux, also called heartburn.
Doctors typically adopt a “wait and watch” approach to treating Barrett’s esophagus because the condition only rarely leads to cancer and is hard to treat surgically.
In the study, Maley and colleagues analyzed precancerous tumor data from 268 patients, including multiple biopsies within each tumor. On average, these patients were followed for 4.4 years, during which time 37 developed cancer.
“We took ecology measures of species diversity and translated them into measures of cell diversity within tumors,” Maley said. The researchers found what they called a striking correlation between cell diversity and progression to cancer: for each additional cell variety detected in a tumor, eventual cancer was twice as likely.
Maley suggested genetically diverse tumors are likelier to generate mutant cells that will flourish and spread, allowing a tumor to transform and grow.
In the future, he added, in addition to serving as a “biomarker” for cancer risk, measures of genetic diversity might help doctors assess the success of cancer prevention therapies.
Genetic diversity among tumor cells might also help explain why therapy sometimes fails, he said. If a tumor contains highly diverse cells, some of those are more likely to resist treatment. Adapting to and surviving chemotherapy, these resistant cells could breed, leading to a cancer relapse.
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