Aspirin, Mortality Link in Breast Cancer May Depend on Methylation of Breast-Cancer Genes

By David Douglas

August 24, 2019

NEW YORK (Reuters Health) - Prior to diagnosis, breast cancer-related genes appear to interact with aspirin in certain women and could influence survival, an observational study hints.

"Consideration of DNA-methylation profiles as potential modifiers of the aspirin-mortality association may provide new biologic insights on the underlying biological mechanisms on aspirin use in relation to mortality after breast-cancer diagnosis," Dr. Tengteng Wang of the University of North Carolina, Chapel Hill, told Reuters Health by email.

She and her colleagues examined data from the population-based Long Island Breast Cancer Study, which involved more than 1,200 women diagnosed between 1996 and 1997.

Prediagnosis aspirin use had been assessed through in-person interviews a mean of 96 days after diagnosis. By the end of 2014, there were 476 all-cause deaths of which 202 were breast-cancer specific.

To determine whether prediagnosis aspirin use might interact with mortality, the researchers examined two global methylation markers in peripheral blood DNA and promoter methylation of a panel of 13 breast cancer-related genes.

All-cause mortality was significantly elevated among aspirin users who had methylated promotor of BRCA1 (hazard ratio, 1.67), but not among those with unmethylated promoter of BRCA (HR, 0.99), the team reports in Cancer, online August 12.

In addition, significantly decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 (HR, 0.60). This was also the case for PR (HR, 0.78) and global hypermethylation of LINE-1 (HR, 0.63).

"Our findings, if confirmed, may also impact clinical decision making by identifying a subgroup of breast-cancer patients, using epigenetic markers, for whom pre-diagnosis aspirin use impacts subsequent mortality; and may help refine risk-reduction strategies to improve survival among women with breast cancer," Dr. Wang said.

In an accompanying editorial Dr. Kristen M. C. Malecki of the University of Wisconsin Madison observes that such studies "although not perfect in establishing causality, are also a critical component of translational research. Translational research aims to move the needle forward by providing evidence to support new clinical treatments, programs, and policies for advancing health."

"Overall," she told Reuters Health by email, "I think the most important finding from this research is that while not without limitations, they begin to ask important questions if individuals will respond differently to a proposed preventive treatment if they have different epigenetic signatures on specific genes related to the disease of interest."


Cancer 2019.