Jacob K Kresovich1,2, Brian T Joyce1,2, Tao Gao1, Yinan Zheng1, Zhou Zhang1, Christopher J Achenbach2,3, Robert L Murphy2,3, Allan C Just4, Jincheng Shen5, Hushan Yang6, Pantel Vokonas7, Joel Schwartz8, Andrea A Baccarelli9, Lifang Hou1,2. 1. Center for Population Epigenetics, Robert H Lurie Comprehensive Cancer Center & Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. 2. Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. 3. Center for Global Health, Institute for Public Health & Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. 4. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 5. Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. 6. Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. 7. VA Normative Aging Study, Veterans Affairs Boston Healthcare System & the Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. 8. Department of Environmental Health, Harvard TH Chan School of Public Health, Harvard University, Boston, MA 02115, USA. 9. Departments of Epidemiology & Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
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.
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.
Entities:
Keywords:
DNA methylation; cancer biomarkers; cancer epigenetics
Authors: Arce Domingo-Relloso; Tianxiao Huan; Karin Haack; Angela L Riffo-Campos; Daniel Levy; M Daniele Fallin; Mary Beth Terry; Ying Zhang; Dorothy A Rhoades; Miguel Herreros-Martinez; Esther Garcia-Esquinas; Shelley A Cole; Maria Tellez-Plaza; Ana Navas-Acien Journal: Clin Epigenetics Date: 2021-02-25 Impact factor: 6.551