Common Mutations Linked To Increased Risk Of Breast Cancer

Women with common variations in the class of enzyme known as glutathione S-transferase (GST), which detoxify carcinogens, have an increased risk of developing breast cancer, according to researchers at the Johns Hopkins School of Public Health. The scientists studied three GST genes, and found that certain genetic variants of the genes increased a woman's odds of developing breast cancer by 1.5 to 2.5 times. Proteins produced by GST genes help the body disarm chemically reactive molecules that can damage cells' DNA and start them on the road to becoming cancerous. The highest change, a nearly fourfold increase in risk, occurred in women with mutations in all three genes.

"This appears to be a significant increase in risk," said Kathy Helzlsouer, MD, associate professor, Epidemiology. "It's definitely not as large as the risk increase associated with genes like BRCA1 or BRCA2, but this genetic variant affects a much larger group of women. One of these genetic variants, for example, is estimated to occur in about 44 percent of the population."

For the study, published in the Journal of the National Cancer Institute, Hopkins scientists compared the genetic makeup of 110 breast cancer patients with 113 women not affected by breast cancer. The women who had breast cancer were more likely to have variations in the GST gene family.

According to Dr. Helzlsouer, if the association can be confirmed with larger studies a substantial proportion of breast cancer cases may be preventible by testing for the genetic variations and then advising women with them to avoid certain environmental cancer risk factors.

The patients and the control subjects were closely matched for age, menopausal status, and age of first period and first pregnancy. Slightly more of the control subjects used estrogen replacement therapy, and each group had similar levels of contraceptive use.

"We had a pretty tight fit between the control and the experimental group," Dr.Helzlsouer said, "but we can't be sure another risk factor isn't affecting our results until researchers can study these connections in a much larger group of patients."

This research was funded by several grants from the National Institutes of Health, including the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Environmental Health Sciences; and the Department of Defense.

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