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Common Mutations Linked to Increased Breast Cancer Risk

Common Mutations Linked to Increased Breast Cancer Risk

Women with common variations in the class of enzyme known as glutathione S-transferase (GST), which detoxify carcinogens, are at increased risk of developing breast cancer, according to researchers at the Johns Hopkins School of Public Health.

The Johns Hopkins scientists found that certain genetic variants of three GST 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.

Significant Increase in Risk

"This appears to be a significant increase in risk," said Kathy Helzlsouer, MD, associate professor of epidem-iology. "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% of the population."

For the study, published in the Journal of the National Cancer Institute, scientists at Johns Hopkins compared the genetic make-up of 110 breast cancer patients with 113 women not affected by breast cancer. They found that 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 by larger studies, a substantial proportion of breast cancer cases may be prevented. Women could be tested for the genetic variations and then advised about avoiding certain environmental cancer risk factors that may trigger their cancer.

The patients and control subjects were closely matched for age, menopausal status, and age of first period and first pregnancy. A slightly larger number of the control subjects used estrogen replacement therapy, and each group had similar rates of contraceptive use.

"We had a pretty tight fit between the control and the experimental group," said Dr. Helzlsouer, "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."

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