title: Genetic disease in the children of Danish survivors of childhood and adolescent cancer.
abstract: OBJECTIVE
  Preconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes.
  
  
  METHODS
  A case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model.
  
  
  RESULTS
  No statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P = .94). A statistically significant association between abdomino-pelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P = .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56).
  
  
  CONCLUSIONS
  Mutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes.
authors: Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. jeanette@cancer.dk
authors: Jeanette F
authors: JF
authors: Winther
authors: Jørgen H
authors: JH
authors: Olsen
authors: Huiyun
authors: H
authors: Wu
authors: Yu
authors: Y
authors: Shyr
authors: John J
authors: JJ
authors: Mulvihill
authors: Marilyn
authors: M
authors: Stovall
authors: Annelise
authors: A
authors: Nielsen
authors: Marianne
authors: M
authors: Schmiegelow
authors: John D
authors: JD
authors: Boice
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000453:epidemiology; D018095:Germ-Line Mutation / Q000187:drug effects / Q000528:radiation effects; D006066:Gonads / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology; D017741:Survivors / Q000706:statistics & numerical data*
chemical_list: D000970:Antineoplastic Agents