title: Telomere content and risk of second malignant neoplasm in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Gramatges
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Okcu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006689:Hodgkin Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies; D017678:Sex Distribution; D017741:Survivors; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult