Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population‐based study

Abstract

BACKGROUND:The authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer. METHODS: Prediagnosis aspirin use was assessed through in-person interviews within a population-based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements-1 (LINE-1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer-related genes was measured in tumor by methylation-specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer-specific/all-cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions. RESULTS: All-cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26-2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67-1.45; P for interaction ≤.05). Decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE-1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null. CONCLUSIONS: The current study suggests that the LINE-1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer. Cancer 2019;125:3836-3844.

Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging

“…Our findings are in accordance with previous studies suggesting that epigenetic modifications are involved in the chemopreventive actions of aspirin. Recently, an association between aspirin use and BRCA1 promoter methylation that affects the mortality after breast cancer has been shown [ 26 ]. Similarly, in mouse inflammation model, aspirin has been shown to reduced tumor multiplicity by suppressing histone deacetylases (HDAC), with concomitant increase of H3K27ac in the promoter regions of pro-inflammatory genes [ 27 ].…”

Low-Dose Aspirin Use Significantly Improves the Survival of Late-Stage NPC: A Propensity Score-Matched Cohort Study in Taiwan

“…The anti-inflammatory properties of aspirin exert favorable effects on managing the challenges of survivorship in various cancers [ 15 , 16 , 17 ]. A prolongation of survival among aspirin users was seen across different tumor types, such as colorectal, gastrointestinal, and other cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In addition, several retrospective studies demonstrated that cancer patients who have taken aspirin might be at a lower risk of developing metastatic cancer [ 21 , 27 ].…”

“…In addition, several retrospective studies demonstrated that cancer patients who have taken aspirin might be at a lower risk of developing metastatic cancer [ 21 , 27 ]. Nevertheless, despite the growing number of randomized controlled trials and meta-analyses of these studies that demonstrate the benefits of aspirin in various cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], the effect of aspirin on NPC has not been explored.…”

“…Our interest in evaluating the potential of aspirin to improve the clinical outcomes of NPC patients increased owing to the fact that it improves the survival and cancer management in patients with other cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. In order to understand whether there is an association between increased survival rates in NPC and aspirin use, we used a database from Chang Gung Memorial Hospital to conduct a cohort study with a long follow-up period (10 years) to analyze overall survival (OS) and disease-specific survival (DSS) rates [ 28 ].…”

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

“…On the basis of the latest global cancer statistics, there was almost 2.1 million newly diagnosed breast cancer patients in 2018, amount to nearly one forth women cancer cases [1]. In the wake of the progress of the era, there has been numerous advanced innovations been exploiting in the early diagnosis and the systematical management of BRCA [4]. Nevertheless, patients with BRCA are still facing a formidable challenge in the light of their undesirable overall survival.…”