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Breast Cancer Research
Published in: Breast Cancer Research 1/2017

Open Access 01-12-2017 | Research article

Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes

Authors: Lauren E. McCullough, Jia Chen, Yoon Hee Cho, Nikhil K. Khankari, Patrick T. Bradshaw, Alexandra J. White, Susan L. Teitelbaum, Mary Beth Terry, Alfred I. Neugut, Hanina Hibshoosh, Regina M. Santella, Marilie D. Gammon

Published in: Breast Cancer Research | Issue 1/2017

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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.
Appendix
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Metadata
Title
Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes
Authors
Lauren E. McCullough
Jia Chen
Yoon Hee Cho
Nikhil K. Khankari
Patrick T. Bradshaw
Alexandra J. White
Susan L. Teitelbaum
Mary Beth Terry
Alfred I. Neugut
Hanina Hibshoosh
Regina M. Santella
Marilie D. Gammon
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2017
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-017-0811-z

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