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Study links breast cancer risk to epigenetic changes related to race, smoking and birth size

April 16, 2007

LOS ANGELES — Women can encounter environmental factors that increase their risk of breast cancer at various periods of their physical development, beginning before birth and extending until menopause. These non-inherited, or epigenetic, changes in DNA can correlate with risk factors for breast cancer, according to research being presented at the 2007 Annual Meeting of the American Association for Cancer Research.

To study the effects of epigenetic changes in DNA, a team of researchers from Columbia University School of Public Health, led by Mary Beth B. Terry, Ph.D., collected information from former participants of the National Collaborative Perinatal Project born between 1959 and 1966.

"We've been following a birth cohort of women who were all born at Columbia in the late 50s and early 60s," said Terry. "We're interested to find if early life factors are associated with breast cancer susceptibility."

The researchers gathered data on childhood and adult exposures, along with blood samples and mammograms, from 263 women. Terry and her colleagues looked at an epigenetic effect called DNA methylation, whereby DNA is tagged by a molecular "methyl" fragment, which alters activation of the genes. In this instance, the researchers looked at global hypomethylation - aberrant methylation throughout the entirety of a person's DNA.

The researchers found differences in global DNA hypomethylation depending on breast cancer risk factors including racial group, smoking status, and infant and childhood size. "Birth size in particular has been correlated with breast cancer later in life, but nobody really knows why," Terry pointed out. "This is a small pilot study to look at one possible mechanism."

Other correlating factors included ethnic group and smoking or nonsmoking status. Twenty-one percent of whites, 39 percent of blacks, and 13 percent of Hispanics were in the highest quartile, while 35 percent current smokers were in the highest quartile compared with 15 percent former smokers and 26 percent of women who never smoked.

The researchers also plan to look at gene-specific hypermethylation in a variety of different genes that might be important for breast cancer, according to Terry.

Terry notes that although this pilot study used a very diverse sample, it was still a relatively small group, and the next step is a much larger study using samples from hundreds of women. Such an effort is currently in progress.

"We're going to try to see if we find these patterns holding up in a much larger sample now," Terry said. "We see this as a first step to understand why measures from birth might be related to adult disease much later in life."

American Association for Cancer Research