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

Publication ,  Journal Article
Ojha, J; Codd, V; Nelson, CP; Samani, NJ; Smirnov, IV; Madsen, NR; Hansen, HM; de Smith, AJ; Bracci, PM; Wiencke, JK; Wrensch, MR; Wiemels, JL ...
Published in: Cancer Epidemiol Biomarkers Prev
July 2016

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.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

July 2016

Volume

25

Issue

7

Start / End Page

1043 / 1049

Location

United States

Related Subject Headings

  • Telomere Homeostasis
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Leukocytes
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

APA
Chicago
ICMJE
MLA
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Ojha, J., Codd, V., Nelson, C. P., Samani, N. J., Smirnov, I. V., Madsen, N. R., … ENGAGE Consortium Telomere Group, . (2016). Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia. Cancer Epidemiol Biomarkers Prev, 25(7), 1043–1049. https://doi.org/10.1158/1055-9965.EPI-15-1329
Ojha, Juhi, Veryan Codd, Christopher P. Nelson, Nilesh J. Samani, Ivan V. Smirnov, Nils R. Madsen, Helen M. Hansen, et al. “Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia.Cancer Epidemiol Biomarkers Prev 25, no. 7 (July 2016): 1043–49. https://doi.org/10.1158/1055-9965.EPI-15-1329.
Ojha J, Codd V, Nelson CP, Samani NJ, Smirnov IV, Madsen NR, et al. Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1043–9.
Ojha, Juhi, et al. “Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia.Cancer Epidemiol Biomarkers Prev, vol. 25, no. 7, July 2016, pp. 1043–49. Pubmed, doi:10.1158/1055-9965.EPI-15-1329.
Ojha J, Codd V, Nelson CP, Samani NJ, Smirnov IV, Madsen NR, Hansen HM, de Smith AJ, Bracci PM, Wiencke JK, Wrensch MR, Wiemels JL, Walsh KM, ENGAGE Consortium Telomere Group. Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1043–1049.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

July 2016

Volume

25

Issue

7

Start / End Page

1043 / 1049

Location

United States

Related Subject Headings

  • Telomere Homeostasis
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Leukocytes
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation