Genetically predicted telomere length is associated with clonal somatic copy number alterations in peripheral leukocytes.

Autor: Brown DW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States of America.; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, United States of America., Lin SH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States of America., Loh PR; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States of America., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States of America., Savage SA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States of America., Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2020 Oct 22; Vol. 16 (10), pp. e1009078. Date of Electronic Publication: 2020 Oct 22 (Print Publication: 2020).
DOI: 10.1371/journal.pgen.1009078
Abstrakt: Telomeres are DNA-protein structures at the ends of chromosomes essential in maintaining chromosomal stability. Observational studies have identified associations between telomeres and elevated cancer risk, including hematologic malignancies; but biologic mechanisms relating telomere length to cancer etiology remain unclear. Our study sought to better understand the relationship between telomere length and cancer risk by evaluating genetically-predicted telomere length (gTL) in relation to the presence of clonal somatic copy number alterations (SCNAs) in peripheral blood leukocytes. Genotyping array data were acquired from 431,507 participants in the UK Biobank and used to detect SCNAs from intensity information and infer telomere length using a polygenic risk score (PRS) of variants previously associated with leukocyte telomere length. In total, 15,236 (3.5%) of individuals had a detectable clonal SCNA on an autosomal chromosome. Overall, higher gTL value was positively associated with the presence of an autosomal SCNA (OR = 1.07, 95% CI = 1.05-1.09, P = 1.61×10-15). There was high consistency in effect estimates across strata of chromosomal event location (e.g., telomeric ends, interstitial or whole chromosome event; Phet = 0.37) and strata of copy number state (e.g., gain, loss, or neutral events; Phet = 0.05). Higher gTL value was associated with a greater cellular fraction of clones carrying autosomal SCNAs (β = 0.004, 95% CI = 0.002-0.007, P = 6.61×10-4). Our population-based examination of gTL and SCNAs suggests inherited components of telomere length do not preferentially impact autosomal SCNA event location or copy number status, but rather likely influence cellular replicative potential.
Competing Interests: The authors declare no competing interests.
Databáze: MEDLINE
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