Get started
Work

Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia

Year: 2016
Type: article
Study design: Observational Study
Abstract: 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 × 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 × 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 × 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. Cancer Epidemiol Biomarkers Prev; 25(7); 1043-9. ©2016 AACR.
DOI: 10.1158/1055-9965.epi-15-1329
Authors: Juhi Ojha, Veryan Codd, Christopher P. Nelson, Nilesh J. Samani, Ivan V. Smirnov, Nils R. Madsen, Helen M. Hansen, Adam J. de Smith, Paige M. Bracci, John K. Wiencke, Margaret R. Wrensch, Joseph L. Wiemels, Kyle M. Walsh
Language: English
Subfield: Hematology
Field: Medicine
Open Access status: green
Funders: Howard Hughes Medical Institute, Sontag Foundation, Wellcome Trust, British Heart Foundation, National Institutes of Health, University of California, San Francisco, Medical Research Council, Horizon 2020, National Human Genome Research Institute, National Cancer Institute
Awards: GM - CSF - producing tumor cell line as a CML vaccine, Large Scale Sequencing and Analysis of Genomes, META-DAC - Managing Ethico-social and Technical issues and Administration of Data Access Committee, WTCCC2 core activities, Biomarkers of survival in glioma epidemiology, Telomere length measurement in UK Biobank: advancing understanding of biological ageing and age-related diseases, G4615298919, G4721365007, International Case Control Study of Malignant Glioma, Pharmacogenomics of cytosine arabinoside (Ara-C) and acute myelogenous leukemia, G8015611077, Genetic and molecular epidemiology of adult glioma, The genetics of weight, BMI, adiposity and obesity, Brain Tumor SPORE Grant
OpenAlex ID: W2370704029
FWCI: 6.391
Cites: 43
Cited by: 74
Related to: 10