Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.

Autor: Cuadros M; Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Av. de la Investigación 11, 18007, Granada, Spain. mcuadros@ugr.es.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007, Granada, Spain. mcuadros@ugr.es.; Health Research Institute of Granada (Ibis.Granada), Av. Fuerzas Armadas 2, 18014, Granada, Spain. mcuadros@ugr.es., Cano C; Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain. ccano@decsai.ugr.es., Garcia-Rodriguez S; Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain. garciarodriguez.sonia@gmail.com.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007, Granada, Spain. garciarodriguez.sonia@gmail.com., Martín JL; Hospital Universitario San Cecilio, Granada, Spain., Poyatos-Andujar A; Hospital Universitario San Cecilio, Granada, Spain., Ruiz-Cabello F; Hospital Virgen de Las Nieves, Granada, Spain., Pedrinaci S; Hospital Virgen de Las Nieves, Granada, Spain., Durán G; Hospital Regional Universitario Carlos Haya, Málaga, Spain., Benavides M; Hospital Regional Universitario Carlos Haya, Málaga, Spain., Bautista-Ojeda MD; Hospital Costa del Sol, Marbella, Spain., Pereda T; Hospital Costa del Sol, Marbella, Spain., Benitez-Cantos MS; Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Av. de la Investigación 11, 18007, Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007, Granada, Spain., Medina P; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007, Granada, Spain.; Health Research Institute of Granada (Ibis.Granada), Av. Fuerzas Armadas 2, 18014, Granada, Spain.; Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. de Fuente Nueva S/N, 18071, Granada, Spain., Blanco A; Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain., Gonzalez A; Instituto de Parasitología y Biomedicina LopezNeyra - CSIC, Granada, Spain., Lizardi P; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007, Granada, Spain.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2022 Mar 04; Vol. 15 (1), pp. 45. Date of Electronic Publication: 2022 Mar 04.
DOI: 10.1186/s12920-022-01183-2
Abstrakt: Background: DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock.
Methods: Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath's DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects.
Results: Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age.
Conclusions: Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers.
(© 2022. The Author(s).)
Databáze: MEDLINE
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