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Published in: Breast Cancer Research and Treatment 2/2017

01-06-2017 | Epidemiology

Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study

Authors: Kathleen Conway, Sharon N. Edmiston, Eloise Parrish, Christopher Bryant, Chiu-Kit Tse, Theresa Swift-Scanlan, Lauren E. McCullough, Pei Fen Kuan

Published in: Breast Cancer Research and Treatment | Issue 2/2017

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Abstract

Purpose

Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression.

Methods

Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status.

Results

Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR- tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites.

Conclusions

Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.
Appendix
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Metadata
Title
Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study
Authors
Kathleen Conway
Sharon N. Edmiston
Eloise Parrish
Christopher Bryant
Chiu-Kit Tse
Theresa Swift-Scanlan
Lauren E. McCullough
Pei Fen Kuan
Publication date
01-06-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4178-8

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