Chemical changes in DNA found in blood and breast cancer tumors may modify aspirin’s role in mortality risk.

August 12, 2019

Previous studies have shown that some women who use aspirin and are later diagnosed with breast cancer may live longer, which may be related to the drug’s anti-inflammatory effects on the body. However, a portion of aspirin users with breast cancer appeared to have a higher risk of death. According to a new study from researchers at the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health, the reason for this reverse effect could be explained by DNA methylation of genes in breast cancer tumors or peripheral blood.

Methylation is a chemical modification wherein a methyl group acts like light switches along the DNA molecule, turning some genetic activity on and some off. Chemical shifts in areas of DNA that are responsible for cell death, damage and repair – such as occurs in methylation – are known contributors to the development of cancer over time. Identifying the areas where these epigenetic changes take place show promise in predicting certain risks or effective methods of treatment.

A new study, published today in the American Cancer Society’s interdisciplinary journal CANCER, is the first to examine the effect of DNA methylation in breast tumor tissues and cells circulating in the patients’ peripheral blood on the association between aspirin use and mortality in women with breast cancer.

Drs. Marilie Gammon and TengTeng Wang

Drs. Marilie Gammon and TengTeng Wang

“Chronic inflammation is a key player in the development of multiple cancer types, including breast cancer,” says first author Tengteng Wang, PhD, who led the study while she was a doctoral candidate in the epidemiology department at the Gillings School. “Aspirin is a major non-steroidal anti-inflammatory drug which has anti-inflammatory properties. Given this, substantial evidence from laboratory and population studies suggests that taking aspirin may reduce the risk of developing breast cancer.”

However, the association of aspirin use with death outcomes following breast cancer diagnosis remains inconclusive and inconsistent across studies, which prompted the researchers to explore whether aspirin’s varying influences on breast cancer patients could be related to distinctly different DNA profiles due to methylation.

The team analyzed data from 1,266 women with breast cancer in the Long Island Breast Cancer Study who were followed for subsequent mortality. All-cause death after breast cancer was elevated by 67% among those who had used aspirin at least once a week for six weeks pre-diagnosis and had a methylated tumor promotor of breast cancer gene 1, known as BRCA1. Breast cancer-specific mortality decreased by 22-40% in aspirin users with an unmethylated tumor promoter of BRCA1 and progesterone receptor (PR) genes, and also in those with long interspersed elements-1 global hypermethylation. These results suggest real differences in breast cancer mortality risk in patient groups with these different methylation profiles in tumor tissue DNA and peripheral blood DNA.

The research team points to the need for further exploration on the potential impact – good or bad – aspirin may have on specific breast cancer patients due to their DNA methylation profiles. The findings do not indicate that anyone with elevated breast cancer risk should start taking aspirin, and people should speak to their doctors before they make changes to their medications.

“Future research designed to replicate our findings should include a larger sample size to allow examination of patterns of aspirin use, and an enlarged panel of genes to explore the role of genetic predisposition in driving overall genetic instability on survival after breast cancer diagnosis,” say Wang and her mentor and co-author, Marilie Gammon, PhD, professor of epidemiology at the Gillings School.

This study was funded in part by grants from the National Institutes of Health and was conducted in collaboration with researchers at Emory University, the University of California at Berkeley, the University of Montana, Columbia University and the Icahn School of Medicine at Mount Sinai, as well as Roche Product Development in Asia-Pacific in Shanghai, China, and the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.

Wang, now a UNC Gillings alumna, currently works as a postdoctoral researcher at Harvard University and Brigham and Women’s Hospital.

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