title: Breast cancer risk after radiotherapy for heritable and non-heritable retinoblastoma: a US-UK study.
abstract: BACKGROUND
  Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors.
  
  
  METHODS
  Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls.
  
  
  RESULTS
  Overall there was no significant variation of breast cancer risk with dose (P>0.5). However, there was a pronounced and significant (P=0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P=0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P=0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P>0.5).
  
  
  CONCLUSIONS
  There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution.
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Little
authors.affiliation: Department of Statistics, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Schaeffer
authors.affiliation: Department of Public Health and Epidemiology, Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Reulen
authors.affiliation: Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Abramson
authors.affiliation: Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Stovall
authors.affiliation: Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Weathers
authors.affiliation: Radiation Epidemiology Group, Unit 1018 INSERM, Institut Gustave Roussy, 98000 Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: de Vathaire
authors.affiliation: Radiation Epidemiology Group, Unit 1018 INSERM, Institut Gustave Roussy, 98000 Villejuif, France.
authors.forename: I
authors.initials: I
authors.lastname: Diallo
authors.affiliation: Ophthalmic Epidemiology and Genetics Service, Tufts-New England Medical Center, Boston, MA 02111, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Seddon
authors.affiliation: Department of Public Health and Epidemiology, Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Hawkins
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Kleinerman
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005134:Eye Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D005260:Female; D016161:Genes, Retinoblastoma; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012175:Retinoblastoma / Q000235:genetics / Q000532:radiotherapy*; D012189:Retrospective Studies; D012306:Risk; D018401:Sample Size; D016037:Single-Blind Method; D017741:Survivors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
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