title: Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood.
abstract: BACKGROUND
  Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment.
  
  
  METHODS
  We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child.
  
  
  RESULTS
  Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially.
  
  
  CONCLUSIONS
  Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.
authors.affiliation: Research Unit of Cancer Epidemiology (U351 INSERM), Villejuif, France.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kony
authors.forename: F
authors.initials: F
authors.lastname: de Vathaire
authors.forename: A
authors.initials: A
authors.lastname: Chompret
authors.forename: A
authors.initials: A
authors.lastname: Shamsaldim
authors.forename: E
authors.initials: E
authors.lastname: Grimaud
authors.forename: M A
authors.initials: MA
authors.lastname: Raquin
authors.forename: O
authors.initials: O
authors.lastname: Oberlin
authors.forename: L
authors.initials: L
authors.lastname: Brugières
authors.forename: J
authors.initials: J
authors.lastname: Feunteun
authors.forename: F
authors.initials: F
authors.lastname: Eschwège
authors.forename: J
authors.initials: J
authors.lastname: Chavaudra
authors.forename: J
authors.initials: J
authors.lastname: Lemerle
authors.forename: C
authors.initials: C
authors.lastname: Bonaïti-Pellié
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000145:classification / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008223:Lymphoma / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D009456:Neurofibromatosis 1 / Q000235:genetics; D016017:Odds Ratio; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D012509:Sarcoma / Q000532:radiotherapy; D009396:Wilms Tumor / Q000532:radiotherapy