Cancer linked to aging DNA repair ability.

Despite decades of progress in learning how chemicals, sunlight, and other environmental factors can increase one's risk of developing cancer, the reasons that some people develop tumors and others do not remain mysterious.

Now, researchers studying people with skin cancer have found new evidence that individuals differ not just in their susceptibility to these factors, but also in their ability to fix damaged genes. In addition, adults lose about 1 percent of their capacity to repair DNA each year, says Lawrence Grossman, a molecular biologist at Johns Hopkins University in Baltimore.

This loss may help explain why aging is a risk factor for cancer, adds Qingyi Wei, a molecular epidemiologist at Johns Hopkins.

Wei, Grossman, and their colleagues studied 88 people with basal cell carcinoma, an easily observed and readily treated cancer. The researchers also looked at DNA repair in 135 individuals with mild skin problems but not skin cancer. All study participants were Caucasians between the ages of 20 and 60. Researchers took blood samples and medical histories from them and asked questions about the number of severe sunburns they had had and the incidence of cancer in their families. Dermatologists evaluated the participants' skin condition.

The researchers then take an unusual approach to assessing an individual's ability to fix broken genes, Grossman says. They inject a small piece of genetic material into white blood cells extracted from each participant. The genetic material contains a mutant bacterial gene that normally codes for an enzyme the white blood cells never make. If the cells fix the gene, the gene then causes the cells to produce the enzyme. Forty hours later, the researchers measure the activity of that enzyme, which signals how well the cells have mended the gene.

The study revealed that young people with this skin cancer had the repair capacity of someone 30 years older. They also tended to have relatives with the disease. "This gives a clue that DNA repair capacity might be genetically linked:' says Wei.

Overall, people with low repair capacity were five times more likely to develop the skin cancer if exposed to intense sun than those who had high repair abilities and stayed out of the sun. Also, women seemed more susceptible than men, especially if they had six or more severe sunburns, the researchers reported in the Feb. 15 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

As one of the first studies to combine laboratory and epidemiological data, "it verifies that effective DNA repair reduces the risk of cancer and that the magnitude [of that reduction] can be quite large:' comments Richard Setlow of Brookhaven National Laboratory in Upton, N.Y

Because o! the body's gradual decline in repair capabilities, the researchers observed little difference in DNA repair capacities of older people. In them, differences in exposure to sunlight seemed critical to determining who developed tumors. "All that damage overcomes the repair system:' says Wei.

"I think what people are starting to understand is that the link between aging and cancer is very, very close:' says late more and more persistent damage." He and his colleagues are now studying DNA repair in people with other types of cancer.

"It's an important paper that demonstrates that DNA repair plays a role in aging, which wasn't really demonstrated before," comments Viihelm Bohr at the National Institute on Aging's Gerontology Research Center in Baltimore.

In addition, the differences between men and women suggest that hormones may influence DNA repair capacity. Grossman notes that, of the female participants, postmenopausal women who were receiving estrogen treatments retained' 25 to 30 percent more repair capacity than other women their age.