ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- Pooled it
- Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.Nature communications · 2018Pooled it
- The spectrum of immunoglobulin heavy chain enhancer hijacking in chronic lymphocytic leukemia.Leukemia · 2026Article
- Genetic Determinants of Telomere Length and Their Role in Human Disease: Molecular Mechanisms and Underrepresented Populations' Perspectives.Biomedicines · 2026Review
- Relative leukocyte telomere length and the risk of lung cancer progression in individuals with pulmonary nodules.BMC medicine · 2026Article
- Telomere Length Abnormality: Investigating Approaches and Correlations with Cancer, Bone Marrow Failure and Hematological Malignancies.Biomedicines · 2025Review
- Causality between Telomere Length and the Risk of Hematologic Malignancies: A Bidirectional Mendelian Randomization Study.Cancer research communications · 2024Article
- Conditional Depletion of STN1 in Mouse Embryonic Fibroblasts.Bio-protocol · 2024Article
- Article
- High Expression of ZNF208 Predicts Better Prognosis and Suppresses the Tumorigenesis of Breast Cancer.Clinical Medicine Insights. Oncology · 2024Article
- Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis.Nature genetics · 2023Article
- CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.Nature communications · 2023Article
- Predicted leukocyte telomere length and risk of myeloid neoplasms.Human molecular genetics · 2023Article
- Role of telomere length in human carcinogenesis (Review).International journal of oncology · 2023Review
- Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair.Science advances · 2023Article
- Review
- Rap1 prevents fusions between long telomeres in fission yeast.The EMBO journal · 2022Article
- Transcriptomic Analysis of Conserved Telomere Maintenance Component 1 (CTC1) and Its Association with Leukemia.Journal of clinical medicine · 2022Article
- Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.Science advances · 2022Article
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundChronic 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.
methodsWe 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
resultsThree 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.
conclusionsGenetic 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.
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