PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Ojha, J.* ; Codd, V.* ; Nelson, C.P.* ; Samani, N.J.* ; Smirnov, I.V.* ; Madsen, N.R.* ; Hansen, H.M.* ; de Smith, A.J.* ; Bracci, P.M.* ; Wiencke, J.K.* ; Wrensch, M.R.* ; Wiemels, J.L.* ; Walsh, K.M.* ; ENGAGE Consortium Telomere Group (Albrecht, E. ; Gieger, C. ; Klopp, N. ; Peters, A. ; Wichmann, H.-E.)

Genetic variation associated with longer telomere length increases risk of chronic lymphocytic leukemia.

Cancer Epidemiol. Biomarkers Prev. 25, 1043-1049 (2016)
Publ. Version/Full Text DOI
Closed
Open Access Green as soon as Postprint is submitted to ZB.
Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility. Methods: We collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case-control comparisons, we analyzed eight SNPs in genes definitively associated with inter-individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1. Results: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15-1.86; P = 1.8 x 10(-3)], TERT (OR = 1.23; 95% CI, 1.02-1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08-1.71; P = 9.6 x 10(-3)). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case-control sets (P = 9.4 x 10(-4) and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination. Conclusions: Genetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis. Impact: A genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
3.622
1.237
33
50
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Mendelian Randomization; Adult Glioma; Cancer; Diagnosis; Disease; Maintenance; Aberrations; Dysfunction; Variants
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1055-9965
e-ISSN 1538-7755
Journal Cancer Epidemiology, Biomarkers & Prevention
Quellenangaben Volume: 25, Issue: 7, Pages: 1043-1049 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place Philadelphia
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-504091-004
G-504000-007
DOI 10.1158/1055-9965.EPI-15-1329
WOS ID WOS:000380072700005
Erfassungsdatum 2016-09-15
[➜Report correction]