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To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and\/or tumor promoter methylation of breast cancer\u2010related genes interact with aspirin use to impact mortality after breast cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prediagnosis aspirin use was assessed through in\u2010person interviews within a population\u2010based 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\u20101 (LINE\u20101) and the luminometric methylation assay. Promoter methylation of 13 breast cancer\u2010related genes was measured in tumor by methylation\u2010specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N\u00a0=\u00a0202\/476 breast cancer\u2010specific\/all\u2010cause 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All\u2010cause mortality was elevated among aspirin users who had methylated promotor of <jats:italic>BRCA1<\/jats:italic> (HR, 1.67; 95% CI, 1.26\u20102.22), but not among those with unmethylated promoter of <jats:italic>BRCA1<\/jats:italic> (HR, 0.99; 95% CI, 0.67\u20101.45; <jats:italic>P<\/jats:italic> for interaction \u2264.05). Decreased breast cancer\u2010specific mortality was observed among aspirin users who had unmethylated promotor of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>PR<\/jats:italic> and global hypermethylation of LINE\u20101 (HR, 0.60, 0.78, and 0.63, respectively; <jats:italic>P<\/jats:italic> for interaction \u2264.05), although the 95% CIs included the null.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current study suggests that the LINE\u20101 global methylation and promoter methylation of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>PR<\/jats:italic> in tumor may interact with aspirin use to influence mortality after breast cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32364","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T03:23:08Z","timestamp":1565580188000},"page":"3836-3844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population\u2010based study"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-186X","authenticated-orcid":false,"given":"Tengteng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology University of North Carolina Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra J.","family":"White","sequence":"additional","affiliation":[{"name":"Epidemiology Branch National Institute of Environmental Health Sciences Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Division of Epidemiology University of California Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biometrics Roche Product Development in Asia\u2010Pacific Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences University of Montana Missoula Montana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Terry","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Teitelbaum","sequence":"additional","affiliation":[{"name":"Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred I.","family":"Neugut","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University New York New York"},{"name":"Department of Medicine Columbia University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina M.","family":"Santella","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[{"name":"Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai 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