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Clin Cancer Res. 2014 Feb 15;20(4):904-11. doi: 10.1158/1078-0432.CCR-13-2076. Epub 2013 Nov 25.

Telomere content and risk of second malignant neoplasm in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

Author information

1
Authors' Affiliations: Texas Children's Cancer Center, Baylor College of Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas; School of Public Health, University of Alberta, Edmonton, Canada; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; St. Jude Children's Research Hospital, Memphis, Tennessee; and City of Hope, Duarte, California.

Abstract

PURPOSE:

Shorter constitutional telomere length has been associated with increased cancer incidence. Furthermore, telomere shortening is observed in response to intensive chemotherapy and/or ionizing radiation exposure. We aimed to determine whether less telomere content was associated with treatment-related second malignant neoplasms (SMN) in childhood cancer survivors.

EXPERIMENTAL DESIGN:

Using a nested case-control design, 147 cancer survivors with breast cancer, thyroid cancer, or sarcoma developing after treatment for childhood cancer (cases) were matched (1:1) with childhood cancer survivors without a SMN (controls). Cases and controls were matched by primary cancer diagnosis, years since diagnosis, age at the time of sample collection, years of follow-up from childhood cancer diagnosis, exposure to specific chemotherapy agents, and to specific radiation fields. We performed conditional logistic regression using telomere content as a continuous variable to estimate ORs with corresponding 95% confidence intervals (CI) for development of SMN. ORs were also estimated for specific SMN types, i.e., breast cancer, thyroid cancer, and sarcoma.

RESULTS:

There was an inverse relationship between telomere content and SMN, with an adjusted OR of 0.3 per unit change in telomere length to single-copy gene ratio (95% CI, 0.09-1.02; P = 0.05). Patients with thyroid cancer SMN were less likely to have more telomere content (OR, 0.04; 95% CI, 0.00-0.55; P = 0.01), but statistically significant associations could not be demonstrated for breast cancer or sarcoma.

CONCLUSIONS:

A relation between less telomere content and treatment-related thyroid cancer was observed, suggesting that shorter telomeres may contribute to certain SMNs in childhood cancer survivors.

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PMID:
24277454
PMCID:
PMC3944671
DOI:
10.1158/1078-0432.CCR-13-2076
[Indexed for MEDLINE]
Free PMC Article

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