Increased epigenetic age in normal breast tissue from luminal breast cancer patients

Erin W. Hofstatter, Steve Horvath, Disha Dalela, Piyush Gupta, Anees B. Chagpar, Vikram B. Wali, Veerle Bossuyt, Anna Maria Storniolo, Christos Hatzis, Gauri Patwardhan, Marie Kristin Von Wahlde, Meghan Butler, Lianne Epstein, Karen Stavris, Tracy Sturrock, Alexander Au, Stephanie Kwei, Lajos Pusztai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Original languageEnglish (US)
Article number112
JournalClinical Epigenetics
Volume10
Issue number1
DOIs
StatePublished - Aug 29 2018
Externally publishedYes

Fingerprint

Epigenomics
Breast
Breast Neoplasms
DNA Methylation
Smoking
Tissue Banks
Mastectomy
Human Genome
Methylation
Multivariate Analysis
Biomarkers
Demography

Keywords

  • Biomarkers
  • Breast
  • Breast neoplasms
  • DNA methylation
  • Epigenetics
  • Epigenomics
  • Genome
  • Humans
  • Multivariate analysis
  • Smoking

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Hofstatter, E. W., Horvath, S., Dalela, D., Gupta, P., Chagpar, A. B., Wali, V. B., ... Pusztai, L. (2018). Increased epigenetic age in normal breast tissue from luminal breast cancer patients. Clinical Epigenetics, 10(1), [112]. https://doi.org/10.1186/s13148-018-0534-8

Increased epigenetic age in normal breast tissue from luminal breast cancer patients. / Hofstatter, Erin W.; Horvath, Steve; Dalela, Disha; Gupta, Piyush; Chagpar, Anees B.; Wali, Vikram B.; Bossuyt, Veerle; Storniolo, Anna Maria; Hatzis, Christos; Patwardhan, Gauri; Von Wahlde, Marie Kristin; Butler, Meghan; Epstein, Lianne; Stavris, Karen; Sturrock, Tracy; Au, Alexander; Kwei, Stephanie; Pusztai, Lajos.

In: Clinical Epigenetics, Vol. 10, No. 1, 112, 29.08.2018.

Research output: Contribution to journalArticle

Hofstatter, EW, Horvath, S, Dalela, D, Gupta, P, Chagpar, AB, Wali, VB, Bossuyt, V, Storniolo, AM, Hatzis, C, Patwardhan, G, Von Wahlde, MK, Butler, M, Epstein, L, Stavris, K, Sturrock, T, Au, A, Kwei, S & Pusztai, L 2018, 'Increased epigenetic age in normal breast tissue from luminal breast cancer patients', Clinical Epigenetics, vol. 10, no. 1, 112. https://doi.org/10.1186/s13148-018-0534-8
Hofstatter EW, Horvath S, Dalela D, Gupta P, Chagpar AB, Wali VB et al. Increased epigenetic age in normal breast tissue from luminal breast cancer patients. Clinical Epigenetics. 2018 Aug 29;10(1). 112. https://doi.org/10.1186/s13148-018-0534-8
Hofstatter, Erin W. ; Horvath, Steve ; Dalela, Disha ; Gupta, Piyush ; Chagpar, Anees B. ; Wali, Vikram B. ; Bossuyt, Veerle ; Storniolo, Anna Maria ; Hatzis, Christos ; Patwardhan, Gauri ; Von Wahlde, Marie Kristin ; Butler, Meghan ; Epstein, Lianne ; Stavris, Karen ; Sturrock, Tracy ; Au, Alexander ; Kwei, Stephanie ; Pusztai, Lajos. / Increased epigenetic age in normal breast tissue from luminal breast cancer patients. In: Clinical Epigenetics. 2018 ; Vol. 10, No. 1.
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abstract = "Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the {"}Epigenetic Clock,{"} a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.",
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T1 - Increased epigenetic age in normal breast tissue from luminal breast cancer patients

AU - Hofstatter, Erin W.

AU - Horvath, Steve

AU - Dalela, Disha

AU - Gupta, Piyush

AU - Chagpar, Anees B.

AU - Wali, Vikram B.

AU - Bossuyt, Veerle

AU - Storniolo, Anna Maria

AU - Hatzis, Christos

AU - Patwardhan, Gauri

AU - Von Wahlde, Marie Kristin

AU - Butler, Meghan

AU - Epstein, Lianne

AU - Stavris, Karen

AU - Sturrock, Tracy

AU - Au, Alexander

AU - Kwei, Stephanie

AU - Pusztai, Lajos

PY - 2018/8/29

Y1 - 2018/8/29

N2 - Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

AB - Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

KW - Biomarkers

KW - Breast

KW - Breast neoplasms

KW - DNA methylation

KW - Epigenetics

KW - Epigenomics

KW - Genome

KW - Humans

KW - Multivariate analysis

KW - Smoking

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