Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.
BMC Med Genomics
; 15(1): 45, 2022 03 04.
Article
en En
| MEDLINE
| ID: mdl-35246124
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales Hereditarias sin Poliposis
/
Metilación de ADN
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Med Genomics
Asunto de la revista:
GENETICA MEDICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
España