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Journal Title:

Breast Cancer Research


Volume 19, Number 1


BioMed Central | 2017-02-21, Pages 19-19

Type of Work:

Article | Final Publisher PDF

Abstract: Background: Mechanisms underlying the inverse association between physical activity and survival after breast cancer are unresolved, but DNA methylation may play a role. We hypothesized that promoter methylation of breast cancer-related genes, as well as global methylation, may modify the association between prediagnostic recreational physical activity RPA and breast cancer mortality.Methods: Using a population-based sample of 1254 women diagnosed with first primary breast cancer, we examined modification of the RPA-mortality association by gene-specific promoter methylation and global methylation. Average lifetime RPA was assessed from menarche to diagnosis through structured in-home interviews. Promoter methylation of 13 breast cancer-related genes was evaluated in archived tumor by methylation-specific polymerase chain reaction and MethyLight assay. Global methylation in white blood cell DNA was determined at long interspersed nucleotide element 1 and by the luminometric methylation assay. After approximately 15 years of follow-up, 486 patients had died, and 186 of the deaths were breast cancer-related. We used Cox proportional hazards regression to estimate HRs and 95% CIs as well as likelihood ratio tests to assess multiplicative interactions.Results: All-cause mortality was lower only among physically active women with methylated promoter of APC HR 0.60, 95% CI 0.40–0.80, CCND2 HR 0.56, 95% CI 0.32–0.99, HIN HR 0.55, 95% CI 0.38–0.80, and TWIST1 HR 0.28, 95% CI 0.14–0.56 in tumors, but not among those with unmethylated tumors significant interaction p < 0.05. We found no interaction between RPA and global methylation.Conclusions: The improved survival after breast cancer that is associated with RPA may be more pronounced in women with promoter tumor methylation in biologically plausible genes.

Subjects: Health Sciences, Epidemiology - Health Sciences, Oncology - Research Funding: This work was supported in part by grants from the National Institutes of Health R25CA057726, U01CA-ES66572, R01CA66572, R01CA109753, 3R01CA109753-04S1, P30ES009089, P30ES10126 and the U.S. Department of Defense BC972772.

This research was also supported in part by the Intramural Research Program of the National Institutes of Health through the National Institute of Environmental Health Sciences.

Keywords: Breast cancer - Epigenetics - Methylation - Physical activity - Survival -

Autor: Lauren McCullough, Jia Chen, Yoon Hee Cho, Nikhil K. Khankari, Patrick T. Bradshaw, Alexandra J. White, Susan L. Teitelbaum, Mary



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