1. Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population‐based study
- Author
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Wang, Tengteng, McCullough, Lauren E, White, Alexandra J, Bradshaw, Patrick T, Xu, Xinran, Cho, Yoon Hee, Terry, Mary Beth, Teitelbaum, Susan L, Neugut, Alfred I, Santella, Regina M, Chen, Jia, and Gammon, Marilie D
- Subjects
Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Genetics ,Cancer ,Breast Cancer ,Prevention ,Good Health and Well Being ,Adult ,Aged ,Anti-Inflammatory Agents ,Non-Steroidal ,Aspirin ,BRCA1 Protein ,Breast Neoplasms ,Cause of Death ,Cohort Studies ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Genetic Predisposition to Disease ,Humans ,Middle Aged ,Population Surveillance ,Prognosis ,Promoter Regions ,Genetic ,aspirin ,breast cancer ,DNA methylation ,epigenetic ,mortality ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Public health - Abstract
BackgroundThe 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.MethodsPrediagnosis 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.ResultsAll-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.ConclusionsThe 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.
- Published
- 2019