Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort

Jacob K. Kresovich, Brian T. Joyce, Tao Gao, Yinan Zheng, Zhou Zhang, Christopher J. Achenbach, Robert L. Murphy, Allan C. Just, Jincheng Shen, Hushan Yang, Pantel Vokonas, Joel Schwartz, Andrea A. Baccarelli, Lifang Hou*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aim: Previous studies suggest telomere shortening represses PGC1A and PGC1B expression leading to mitochondrial dysfunction. Methylation of CpG sites within these genes may interact with these factors to affect cancer risk. Materials & methods: Among 385 men, we identified 84 incidents of cancers (predominantly prostate and nonmelanoma skin). We examined associations between leukocyte DNA methylation of 41 CpGs from PGC1A and PGC1B with telomere length, mitochondrial 8-OHdG lesions, mitochondrial abundance and cancer incidence. Results: Methylation of five and eight CpG sites were significantly associated with telomere length and mitochondrial abundance at p < 0.05. Two CpG sites were independently associated with cancer risk: cg27514608 (PGC1A, TSS1500; HR: 1.55, 95% CI: 1.19-2.03, FDR = 0.02), and cg15219393 (PGC1B, first exon/5′UTR; HR: 3.71, 95% CI: 1.82-7.58, FDR < 0.01). Associations with cg15219393 were observed primarily among men with shorter leukocyte telomeres. Conclusion: PGC1A and PGC1B methylation may serve as early biomarkers of cancer risk.

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalEpigenomics
Volume10
Issue number6
DOIs
StatePublished - Jun 2018

Fingerprint

Telomere
Veterans
Methylation
Incidence
Leukocytes
Telomere Shortening
Neoplasms
DNA Methylation
Tumor Biomarkers
Exons
Prostatic Neoplasms
Skin
Genes

Keywords

  • DNA methylation
  • cancer biomarkers
  • cancer epigenetics

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Kresovich, Jacob K. ; Joyce, Brian T. ; Gao, Tao ; Zheng, Yinan ; Zhang, Zhou ; Achenbach, Christopher J. ; Murphy, Robert L. ; Just, Allan C. ; Shen, Jincheng ; Yang, Hushan ; Vokonas, Pantel ; Schwartz, Joel ; Baccarelli, Andrea A. ; Hou, Lifang. / Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort. In: Epigenomics. 2018 ; Vol. 10, No. 6. pp. 733-743.
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title = "Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort",
abstract = "Aim: Previous studies suggest telomere shortening represses PGC1A and PGC1B expression leading to mitochondrial dysfunction. Methylation of CpG sites within these genes may interact with these factors to affect cancer risk. Materials & methods: Among 385 men, we identified 84 incidents of cancers (predominantly prostate and nonmelanoma skin). We examined associations between leukocyte DNA methylation of 41 CpGs from PGC1A and PGC1B with telomere length, mitochondrial 8-OHdG lesions, mitochondrial abundance and cancer incidence. Results: Methylation of five and eight CpG sites were significantly associated with telomere length and mitochondrial abundance at p < 0.05. Two CpG sites were independently associated with cancer risk: cg27514608 (PGC1A, TSS1500; HR: 1.55, 95{\%} CI: 1.19-2.03, FDR = 0.02), and cg15219393 (PGC1B, first exon/5′UTR; HR: 3.71, 95{\%} CI: 1.82-7.58, FDR < 0.01). Associations with cg15219393 were observed primarily among men with shorter leukocyte telomeres. Conclusion: PGC1A and PGC1B methylation may serve as early biomarkers of cancer risk.",
keywords = "DNA methylation, cancer biomarkers, cancer epigenetics",
author = "Kresovich, {Jacob K.} and Joyce, {Brian T.} and Tao Gao and Yinan Zheng and Zhou Zhang and Achenbach, {Christopher J.} and Murphy, {Robert L.} and Just, {Allan C.} and Jincheng Shen and Hushan Yang and Pantel Vokonas and Joel Schwartz and Baccarelli, {Andrea A.} and Lifang Hou",
year = "2018",
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Kresovich, JK, Joyce, BT, Gao, T, Zheng, Y, Zhang, Z, Achenbach, CJ, Murphy, RL, Just, AC, Shen, J, Yang, H, Vokonas, P, Schwartz, J, Baccarelli, AA & Hou, L 2018, 'Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort', Epigenomics, vol. 10, no. 6, pp. 733-743. https://doi.org/10.2217/epi-2017-0141

Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort. / Kresovich, Jacob K.; Joyce, Brian T.; Gao, Tao; Zheng, Yinan; Zhang, Zhou; Achenbach, Christopher J.; Murphy, Robert L.; Just, Allan C.; Shen, Jincheng; Yang, Hushan; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.; Hou, Lifang.

In: Epigenomics, Vol. 10, No. 6, 06.2018, p. 733-743.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort

AU - Kresovich, Jacob K.

AU - Joyce, Brian T.

AU - Gao, Tao

AU - Zheng, Yinan

AU - Zhang, Zhou

AU - Achenbach, Christopher J.

AU - Murphy, Robert L.

AU - Just, Allan C.

AU - Shen, Jincheng

AU - Yang, Hushan

AU - Vokonas, Pantel

AU - Schwartz, Joel

AU - Baccarelli, Andrea A.

AU - Hou, Lifang

PY - 2018/6

Y1 - 2018/6

N2 - Aim: Previous studies suggest telomere shortening represses PGC1A and PGC1B expression leading to mitochondrial dysfunction. Methylation of CpG sites within these genes may interact with these factors to affect cancer risk. Materials & methods: Among 385 men, we identified 84 incidents of cancers (predominantly prostate and nonmelanoma skin). We examined associations between leukocyte DNA methylation of 41 CpGs from PGC1A and PGC1B with telomere length, mitochondrial 8-OHdG lesions, mitochondrial abundance and cancer incidence. Results: Methylation of five and eight CpG sites were significantly associated with telomere length and mitochondrial abundance at p < 0.05. Two CpG sites were independently associated with cancer risk: cg27514608 (PGC1A, TSS1500; HR: 1.55, 95% CI: 1.19-2.03, FDR = 0.02), and cg15219393 (PGC1B, first exon/5′UTR; HR: 3.71, 95% CI: 1.82-7.58, FDR < 0.01). Associations with cg15219393 were observed primarily among men with shorter leukocyte telomeres. Conclusion: PGC1A and PGC1B methylation may serve as early biomarkers of cancer risk.

AB - Aim: Previous studies suggest telomere shortening represses PGC1A and PGC1B expression leading to mitochondrial dysfunction. Methylation of CpG sites within these genes may interact with these factors to affect cancer risk. Materials & methods: Among 385 men, we identified 84 incidents of cancers (predominantly prostate and nonmelanoma skin). We examined associations between leukocyte DNA methylation of 41 CpGs from PGC1A and PGC1B with telomere length, mitochondrial 8-OHdG lesions, mitochondrial abundance and cancer incidence. Results: Methylation of five and eight CpG sites were significantly associated with telomere length and mitochondrial abundance at p < 0.05. Two CpG sites were independently associated with cancer risk: cg27514608 (PGC1A, TSS1500; HR: 1.55, 95% CI: 1.19-2.03, FDR = 0.02), and cg15219393 (PGC1B, first exon/5′UTR; HR: 3.71, 95% CI: 1.82-7.58, FDR < 0.01). Associations with cg15219393 were observed primarily among men with shorter leukocyte telomeres. Conclusion: PGC1A and PGC1B methylation may serve as early biomarkers of cancer risk.

KW - DNA methylation

KW - cancer biomarkers

KW - cancer epigenetics

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