title: Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.
abstract: BACKGROUND
  The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.
  
  
  METHODS
  Participants included 1996 survivors who previously received treatment for cancer at St. Jude Children's Research Hospital and who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Obesity was defined as a body mass index ≥30 kg/m(2) . The factors associated with adult obesity were identified by subgroup-specific (cranial radiation [CRT] exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific, exploratory, genome-wide association analyses using a 2-stage resampling approach with a type I error rate of 5 × 10(-6) .
  
  
  RESULTS
  Forty-seven percent of survivors who received CRT and 29.4% of those who did not receive CRT were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of CRT status (P < .0001). The odds of obesity were increased among survivors who received CRT who had also received glucocorticoids (P = .014) or who were younger at diagnosis (P = .013). Among the survivors who had received CRT, 166 SNPs were associated with obesity. The strongest association was observed with reference SNP rs35669975 (P = 3.3 × 10(-8) ) on segment 33.3 of the long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A (family with sequence similarity 155, member A). SNPs within the glycine receptor α3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and cadherin 18 type 2 (CDH18) genes also were identified. These genes have been implicated in neural growth, repair, and connectivity.
  
  
  CONCLUSIONS
  Obesity in childhood cancer survivors remains associated with previous exposure to CRT and glucocorticoids. Genetic variants related to neural connectivity may modify the risk of obesity among survivors who receive CRT. Validation of these findings in independent cohorts is required.
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Wilson
authors.affiliation: Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Rohit P
authors.initials: RP
authors.lastname: Ojha
authors.affiliation: Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Neale
authors.affiliation: Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.|School of Public Health, Division of Epidemiology, Biostatistics, and Environmental Health Sciences, University of Memphis, Memphis, Tennessee.
authors.forename: James G
authors.initials: JG
authors.lastname: Gurney
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.|Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006776:Hospitals, Pediatric; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D011110:Polymorphism, Genetic; D017741:Survivors; D014481:United States
keywords: childhood cancer survivor; late effects; obesity; polymorphism