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Could Difference in a Protein Mean Higher Rates of Cancer for African Americans?

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One protein could hinder treatment for over 60,000 African American cancer patients each year.

The death rate for African Americans for all cancers is consistently higher than other cancer patients—18 percent higher for women and 35 percent for men. Although many factors contribute to this disparity, recent results from a lab directed by Joann Sweasy at Yale University indicate that researchers should look closely at a protein called DNA polymerase beta.

Polymerase beta is a naturally occurring enzyme in all humans, but Sweasy’s research indicates that populations originating from Africa may have a different version. “It’s important in terms of the history of human beings and in addressing health disparity questions,” says Sweasy.

Even if you do not smoke and wear suntan lotion, your body’s basic operations, merely processing sugars required for life, can create errors in your genetic code—10 to 20,000 per cell per day. If the errors occur in the wrong place, a normal cell can become a cancer cell and start rapidly producing others like itself. Polymerase beta works as a DNA repairman, finding and correcting these errors.

Researchers believe an abnormal version of the protein could cause cancer, since such versions appear in human prostate, breast, and gastric cancer tumors. “There are drivers and there are hitchhikers,” says Sweasy, regarding the variant protein’s cancer-creating role. “Polymerase beta is likely a driver.”

The difference between the tumor-version of the protein, and the standard type found in the rest of the body, might also be key in treatments such as chemotherapy, which work by overwhelming tumor cells with genetic errors, causing self-destruction.

Yet Sweasy’s study, published in the May edition of DNA Repair, found variants somewhere else.

By looking at this enzyme in blood samples from the National Institute of General Medical Sciences Human Genetic Cell Repository, Sweasy’s lab was able to analyze polymerase beta in 2,400 individuals from around the world. Though the majority of the world had the same “ancestral” version of the protein, populations originating from Africa had a great number of variants.

A polymerase beta variant throughout the body could mean a less-efficient DNA repairman. Such variants could increase the chance for getting cancer and also allow therapies, meant to overwhelm only cancer cells, to overwhelm a patient’s entire body.

Sweasy believes that eventually doctors will treat cancer in the same way they currently treat AIDS—using multiple drugs that work on multiple processes.

Dr. Samuel H. Wilson, former acting director of the National Institute of Environmental Health, finds Sweasy’s work promising, but stresses the need for more research. “The results are interesting and encouraging, but there is still a lot of work to do.”

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