title: Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study.
abstract: BACKGROUND
  Survivors of malignant disease in childhood who have had radiotherapy to the head, neck, or upper thorax have an increased risk of subsequent primary thyroid cancer, but the magnitude of risk over the therapeutic dose range has not been well established. We aimed to quantify the long-term risk of thyroid cancer after radiotherapy and chemotherapy.
  
  
  METHODS
  In a nested case-control study, 69 cases with pathologically confirmed thyroid cancer and 265 matched controls without thyroid cancer were identified from 14,054 5-year survivors of cancer during childhood from the Childhood Cancer Survivor Study cohort. Childhood cancers were diagnosed between 1970 and 1986 with cohort follow-up to 2000.
  
  
  RESULTS
  Risk of thyroid cancer increased with radiation doses up to 20-29 Gy (odds ratio 9.8 [95% CI 3.2-34.8]). At doses greater than 30 Gy, a fall in the dose-response relation was seen. Both the increased and decreased risks were more pronounced in those diagnosed with a first primary malignant disease before age 10 years than in those older than 10 years. Furthermore, the fall in risk remained when those diagnosed with Hodgkin's lymphoma were excluded. Chemotherapy for the first cancer was not associated with thyroid-cancer risk, and it did not modify the effect of radiotherapy. 29 (42%) cases had a first diagnosis of Hodgkin's lymphoma compared with 49 (19%) controls. 11 (42%) of those who had Hodgkin's lymphoma had subsequent thyroid cancers smaller than 1 cm compared with six (17%) of those who had other types of childhood cancer (p=0.07).
  
  
  CONCLUSIONS
  The reduction in radiation dose-response for risk of thyroid cancer after childhood exposure to thyroid doses higher than 30 Gy is consistent with a cell-killing effect. Standard long-term follow-up of patients who have had Hodgkin's lymphoma for detection of thyroid cancer should also be undertaken for survivors of any cancer during childhood who received radiotherapy to the thorax or head and neck region.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7238, USA. sigurdsa@mail.nih.gov
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
authors.forename: Cécile M
authors.initials: CM
authors.lastname: Ronckers
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Roger L
authors.initials: RL
authors.lastname: Berkow
authors.forename: Sue
authors.initials: S
authors.lastname: Hammond
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
authors.forename: Anna T
authors.initials: AT
authors.lastname: Meadows
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Peter D
authors.initials: PD
authors.lastname: Inskip
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D009381:Neoplasms, Radiation-Induced; D016609:Neoplasms, Second Primary / Q000209:etiology; D011879:Radiotherapy Dosage; D013961:Thyroid Gland / Q000528:radiation effects*; D013964:Thyroid Neoplasms / Q000209:etiology*