Kathleen Conway1,2, Sharon N Edmiston3, Eloise Parrish3, Christopher Bryant4, Chiu-Kit Tse5, Theresa Swift-Scanlan6,7, Lauren E McCullough8, Pei Fen Kuan9. 1. Department of Epidemiology, School of Public Health, University of North Carolina, Campus Box 7435, Chapel Hill, NC, 27599, USA. kconway@med.unc.edu. 2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA. kconway@med.unc.edu. 3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA. 4. Department of Biostatistics, School of Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA. 5. Department of Epidemiology, School of Public Health, University of North Carolina, Campus Box 7435, Chapel Hill, NC, 27599, USA. 6. School of Nursing, Virginia Commonwealth University, Richmond, VA, 23298, USA. 7. Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298, USA. 8. Department of Epidemiology, School of Public Health, Emory University, Atlanta, GA, 30322, USA. 9. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, 11794-3600, USA.
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.
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.
Entities:
Keywords:
Breast cancer; Breast tumor; Epigenetic; Methylation; Smoking
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