DNA methylation age is elevated in breast tissue of healthy women

Mary E. Sehl, Jill E. Henry, Anna Maria Storniolo, Patricia A. Ganz, Steve Horvath

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the “epigenetic clock.” However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. Methods: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. Results: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10−11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = −0.53, p = 4.4 × 10−4). Conclusions: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Mar 31 2017

Fingerprint

DNA Methylation
Breast
Epigenomics
Tissue Banks
Human Body
Healthy Volunteers
Biomarkers
Hormones

Keywords

  • Biomarker of aging
  • Breast cancer
  • Cell cycling
  • DNA methylation
  • Epigenetics
  • Estrogen
  • Tissue aging

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

DNA methylation age is elevated in breast tissue of healthy women. / Sehl, Mary E.; Henry, Jill E.; Storniolo, Anna Maria; Ganz, Patricia A.; Horvath, Steve.

In: Breast Cancer Research and Treatment, 31.03.2017, p. 1-11.

Research output: Contribution to journalArticle

Sehl, Mary E. ; Henry, Jill E. ; Storniolo, Anna Maria ; Ganz, Patricia A. ; Horvath, Steve. / DNA methylation age is elevated in breast tissue of healthy women. In: Breast Cancer Research and Treatment. 2017 ; pp. 1-11.
@article{ff8559cc3c53492085170b395a7767c0,
title = "DNA methylation age is elevated in breast tissue of healthy women",
abstract = "Background: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the “epigenetic clock.” However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. Methods: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. Results: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10−11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = −0.53, p = 4.4 × 10−4). Conclusions: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.",
keywords = "Biomarker of aging, Breast cancer, Cell cycling, DNA methylation, Epigenetics, Estrogen, Tissue aging",
author = "Sehl, {Mary E.} and Henry, {Jill E.} and Storniolo, {Anna Maria} and Ganz, {Patricia A.} and Steve Horvath",
year = "2017",
month = "3",
day = "31",
doi = "10.1007/s10549-017-4218-4",
language = "English (US)",
pages = "1--11",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",

}

TY - JOUR

T1 - DNA methylation age is elevated in breast tissue of healthy women

AU - Sehl, Mary E.

AU - Henry, Jill E.

AU - Storniolo, Anna Maria

AU - Ganz, Patricia A.

AU - Horvath, Steve

PY - 2017/3/31

Y1 - 2017/3/31

N2 - Background: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the “epigenetic clock.” However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. Methods: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. Results: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10−11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = −0.53, p = 4.4 × 10−4). Conclusions: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.

AB - Background: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the “epigenetic clock.” However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. Methods: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. Results: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10−11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = −0.53, p = 4.4 × 10−4). Conclusions: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.

KW - Biomarker of aging

KW - Breast cancer

KW - Cell cycling

KW - DNA methylation

KW - Epigenetics

KW - Estrogen

KW - Tissue aging

UR - http://www.scopus.com/inward/record.url?scp=85016502490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016502490&partnerID=8YFLogxK

U2 - 10.1007/s10549-017-4218-4

DO - 10.1007/s10549-017-4218-4

M3 - Article

C2 - 28364215

AN - SCOPUS:85016502490

SP - 1

EP - 11

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

ER -