Telomere content and risk of second malignant neoplasm in survivors of childhood cancer: A report from the childhood cancer survivor study

Maria M. Gramatges, Qi Liu, Yutaka Yasui, M. Fatih Okcu, Joseph P. Neglia, Louise C. Strong, Gregory T. Armstrong, Leslie L. Robison, Smita Bhatia

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29 Scopus citations


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 treatmentrelated 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 cancerSMNwere 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.

Original languageEnglish (US)
Pages (from-to)904-911
Number of pages8
JournalClinical Cancer Research
Issue number4
StatePublished - 2014


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