Skin cells may provide early warning for cancer risk elsewhere in body

30 October 2009

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While some scientists have argued that cancer is such a complex genetic disease that you'd have to sequence a person's complete genome in order to predict his or her cancer risk, a University of California, Berkeley, cell biologist suggests that the risk may be more simply determined by inexpensively culturing a few skin cells.

Harry Rubin, professor emeritus of molecular and cell biology at UC Berkeley, acknowledges that cancer cells have mutations in hundreds of genes, making it hard to determine which are the key triggers and making prognosis and treatment equally difficult. Even normal tissue differs from person to person because of a myriad of less disruptive mutations and because of different environmental exposures, both of which affect future cancer risk.

But in the September issue of the journal Cancer Epidemiology, Biomarkers and Prevention, Rubin argues that, while it may be hard to dissect the role of each of these mutations, their collective effect should be observable in tissue before any cancers develop.

Specifically, increases in how densely the cells grow, which Rubin argues are a prelude to cancer, may be detectable even before the cancer appears, warning of risks that could be lessened by behavioural changes.

"Over a 50-year career, I've worked with cells transforming (into cancer) in culture and seen the first step in a dynamic way, seen cells continuing to multiply when they should have stopped," Rubin said. "This is the first step in cancer, though not yet cancer, and you can measure these changes quantitatively."

The problem, of course, is that it is impractical to test all the body's tissues to determine whether they have abnormal cell growth. But Rubin has found evidence from other studies that, in some cases, skin fibroblasts show these early changes even before cancer appears in other tissues, such as the colon.

"The abnormal growth behaviour of skin fibroblasts in cancer-prone individuals has suggested that, at least in some cases, cancer can be considered a systemic disease and that this difference in the behaviour of skin fibroblast cells from such individuals may be a practical basis for prevention, diagnosis and management of the disease," he concluded in his paper.

"It's a great idea, scientifically; the question is, 'Is it there clinically?'" said Douglas Brash, professor of therapeutic radiology, genetics and dermatology at Yale School of Medicine. "This is interesting enough that someone should look to see whether it is clinically reliable."

Dr Stuart H. Yuspa, co-chief of the Laboratory of Cancer Biology and Genetics at the National Cancer Institute, agreed. "Harry's ideas are always amazing, and I admired the paper," he said. "His idea has scientific support, and if it turned out to be correct, it could be extremely valuable for people, assuming they would want to know their risk."

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