RT Journal Article
T1 Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.
A1 Cuadros, Marta
A1 Cano, Carlos
A1 Garcia-Rodriguez, Sonia
A1 Martin, Jose Luis
A1 Poyatos-Andujar, Antonio
A1 Ruiz-Cabello, Francisco
A1 Pedrinaci, Susana
A1 Duran, Gema
A1 Benavides, Manuel
A1 Bautista-Ojeda, Maria Dolores
A1 Pereda, Teresa
A1 Benitez-Cantos, Maria Soledad
A1 Medina, Pedro
A1 Blanco, Armando
A1 Gonzalez, Antonio
A1 Lizardi, Paul
K1 DNA methylation
K1 Epigenetic clock
K1 Lynch syndrome
AB 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. 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. 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. 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.
PB BioMed Central
YR 2022
FD 2022-03-04
LK http://hdl.handle.net/10668/20312
UL http://hdl.handle.net/10668/20312
LA en
NO Cuadros M, Cano C, Garcia-Rodriguez S, Martín JL, Poyatos-Andujar A, Ruiz-Cabello F, et al. Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers. BMC Med Genomics. 2022 Mar 4;15(1):45
NO The research leading to these results has received funding from “la Caixa”Foundation (Ref: CAIXA2017/1) for library preparation, sequencing, andemployment of research personnel, from The Fundación Progreso y Salud,Junta de Andalucía, Spain and from DPI2017-84439-R of MINECO, Madridand FEDER for sequencing and employment of research personnel. Finally,grant ref. A-BIO-470-UGR20 from University of Granada and FEDER has funded article processing charges (APC) and sample processing expenses.This work has been carried out as part of Projects CAIXA2017/1 of “la Caixa” Foundation, and DPI2017-84439-R of MINECO, Madrid and FEDERand A-BIO470-UGR20 of University of Granada and FEDER
DS RISalud
RD Apr 12, 2025