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DNA methylation modifies the association between obesity and survival after breast cancer diagnosis

Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women di... Full description

Journal Title: Breast Cancer Research and Treatment 2016, Vol.156(1), pp.183-194
Main Author: McCullough, Lauren
Other Authors: Chen, Jia , Cho, Yoon , Khankari, Nikhil , Bradshaw, Patrick , White, Alexandra , Garbowski, Gail , Teitelbaum, Susan , Terry, Mary , Neugut, Alfred , Hibshoosh, Hanina , Santella, Regina , Gammon, Marilie
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0167-6806 ; E-ISSN: 1573-7217 ; DOI: 10.1007/s10549-016-3724-0
Link: http://dx.doi.org/10.1007/s10549-016-3724-0
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recordid: springer_jour10.1007/s10549-016-3724-0
title: DNA methylation modifies the association between obesity and survival after breast cancer diagnosis
format: Article
creator:
  • McCullough, Lauren
  • Chen, Jia
  • Cho, Yoon
  • Khankari, Nikhil
  • Bradshaw, Patrick
  • White, Alexandra
  • Garbowski, Gail
  • Teitelbaum, Susan
  • Terry, Mary
  • Neugut, Alfred
  • Hibshoosh, Hanina
  • Santella, Regina
  • Gammon, Marilie
subjects:
  • Body mass index
  • Epigenetics
  • Methylation
  • Breast cancer
  • Survival
ispartof: Breast Cancer Research and Treatment, 2016, Vol.156(1), pp.183-194
description: Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up ( N  = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43–4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43–12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19–2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45–4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
language: eng
source:
identifier: ISSN: 0167-6806 ; E-ISSN: 1573-7217 ; DOI: 10.1007/s10549-016-3724-0
fulltext: fulltext
issn:
  • 1573-7217
  • 15737217
  • 0167-6806
  • 01676806
url: Link


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titleDNA methylation modifies the association between obesity and survival after breast cancer diagnosis
creatorMcCullough, Lauren ; Chen, Jia ; Cho, Yoon ; Khankari, Nikhil ; Bradshaw, Patrick ; White, Alexandra ; Garbowski, Gail ; Teitelbaum, Susan ; Terry, Mary ; Neugut, Alfred ; Hibshoosh, Hanina ; Santella, Regina ; Gammon, Marilie
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subjectBody mass index ; Epigenetics ; Methylation ; Breast cancer ; Survival
descriptionMechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up ( N  = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43–4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43–12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19–2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45–4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
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titleDNA methylation modifies the association between obesity and survival after breast cancer diagnosis
descriptionMechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up ( N  = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43–4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43–12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19–2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45–4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
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abstractMechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up ( N  = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43–4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43–12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19–2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45–4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
copNew York
pubSpringer US
doi10.1007/s10549-016-3724-0
pages183-194
date2016-02