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Man TK, Aubert G, Richard MA, et al. Short NK and naïve T-cell telomere length is associated with thyroid cancer in childhood cancer survivors: A report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev. 2021;doi: 10.1158/1055-9965.EPI-21-0791.
Man, T. K., Aubert, G., Richard, M. A., LeJeune, W., Hariri, E., Goltsova, T., Gaikwad, A., Chen, Y., Whitton, J., Leisenring, W. M., Arnold, M. A., Neglia, J. P., Yasui, Y., Robison, L. L., Armstrong, G. T., Bhatia, S., & Gramatges, M. M. (2021). Short NK and naïve T-cell telomere length is associated with thyroid cancer in childhood cancer survivors: A report from the Childhood Cancer Survivor Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, . https://doi.org/10.1158/1055-9965.EPI-21-0791
Man, Tsz-Kwong, et al. "Short NK and naïve T-cell telomere length is associated with thyroid cancer in childhood cancer survivors: A report from the Childhood Cancer Survivor Study." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology vol. (2021). doi: https://doi.org/10.1158/1055-9965.EPI-21-0791
Man TK, Aubert G, Richard MA, LeJeune W, Hariri E, Goltsova T, Gaikwad A, Chen Y, Whitton J, Leisenring WM, Arnold MA, Neglia JP, Yasui Y, Robison LL, Armstrong GT, Bhatia S, Gramatges MM. Short NK and naïve T-cell telomere length is associated with thyroid cancer in childhood cancer survivors: A report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev. 2021 Nov 15; doi: 10.1158/1055-9965.EPI-21-0791. Epub 2021 Nov 15. PMID: 34782395.
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Cancer Epidemiol Biomarkers Prev. 2021 Nov 15; doi: 10.1158/1055-9965.EPI-21-0791. Epub 2021 Nov 15.

Short NK and naïve T-cell telomere length is associated with thyroid cancer in childhood cancer survivors: A report from the Childhood Cancer Survivor Study.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Tsz-Kwong Man, Geraldine Aubert, Melissa A Richard, Wanda LeJeune, Elmira Hariri, Tatiana Goltsova, Amos Gaikwad, Yan Chen, Jillian Whitton, Wendy M Leisenring, Michael A Arnold, Joseph P Neglia, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Smita Bhatia, Maria M Gramatges

Affiliations

  1. Department of Pediatrics, Baylor College of Medicine.
  2. Terry Fox Laboratory, British Columbia Cancer Agency.
  3. Repeat Diagnostics.
  4. School of Public Health, University of Alberta.
  5. Clinical Research and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center.
  6. Department of Pathology and Laboratory Medicine, Children's Hospital Colorado.
  7. Department of Pediatrics, University of Minnesota.
  8. St. Jude Children's Research Hospital.
  9. Institute for Cancer Outcomes and Survivorship and Division of Pediatric Hematology-Oncology, University of Alabama at Birmingham.
  10. Department of Pediatrics, Baylor College of Medicine [email protected].

PMID: 34782395 DOI: 10.1158/1055-9965.EPI-21-0791

Abstract

BACKGROUND: Survivors of childhood cancer are at risk for therapy-related subsequent malignant neoplasms (SMN), including thyroid SMN. Telomere length (TL) is associated with cancer risk, but the relationship between TL and SMN risk among survivors is less clear.

METHODS: We conducted a nested, matched case-control study of radiation-exposed 15-year+ adult survivors of childhood cancer with thyroid SMN (cases) and without SMN (controls). 46 cases were matched to 46 controls by primary diagnosis, chemotherapy (yes/no), radiation field, and follow-up duration. Lymphocyte TL (LTL) was measured by telomere flow-FISH cytometry using blood samples banked at a mean of 38.9 years (cases), 39.2 years (controls). Genetic variation in telomere genes was assessed by whole genome sequencing. Point estimates for LTL <10th percentile were determined for cases and controls.

RESULTS: Cases had shorter median LTL than controls in three out of four leukocyte subsets. Cases were more likely to have NK cell LTL <10th percentile (p=0.01), and 2.8-fold more likely to have naïve T-cell LTL <10th percentile than controls (CI 1.07, 8.78). Five out of 15 cases with a rare indel or missense variant had naïve T-cell LTL <10th percentile, compared with one out of 8 controls.

CONCLUSIONS: Long-term survivors have shorter than expected LTL, a finding that is more pronounced among survivors with thyroid SMN.

IMPACT: The long-term impact of childhood cancer treatment on immune function is poorly understood. Our findings support immune function studies in larger survivor cohorts to assess long-term deficits in adaptive and innate immunity that may underlie SMN risk.

Copyright ©2021, American Association for Cancer Research.

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