title: Genetic variation and bone mineral density in long-term adult survivors of childhood cancer.
abstract: Despite similarities in upfront treatment of childhood cancer, not every adult survivor of childhood cancer (CCS) has an impaired bone mineral density (BMD). No data are available on the role of genetic variation on impairment of BMD in CCS.
  
  
  
  This cross-sectional single-center cohort study included 334 adult CCSs (median follow-up time after cessation of treatment: 15 years; median age at follow-up: 26 years). Total body BMD (BMDTB) and lumbar spine BMD (BMDLS) were measured by dual x-ray absorptiometry. We selected 12 candidate single-nucleotide polymorphisms (SNPs) in 11 genes (COL1A1, TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1, WLS, LRP5, MTHFR, MTRR, IL-6).
  
  
  
  Multivariate analyses revealed that lower BMD was associated with lower weight and height at follow-up, male sex, and previously administered radiotherapy. Survivors with the homozygous minor allele (GG) genotype of rs2504063 (ESR1: estrogen receptor type 1) had a lower BMDTBvalues (-1.16 vs. -0.82; P = 0.01) than those with the AG/AA genotype; however, BMDLSwas not different. Carriers of two minor alleles (GG) of rs599083 (LRP5: low-density lipoprotein receptor) revealed lower BMDTB(-1.20 vs. -0.78; P = 0.02) and lower BMDLS(-0.95 vs. -0.46; P = 0.01) values than those with the TT/TG genotype.
  
  
  
  CCSs who are carriers of candidate SNPs in the ESR1 or LRP5 genes seem to have an impaired bone mass at an early adult age. Information on genetic variation, in addition to patient- and treatment-related factors, may be helpful in identifying survivors who are at risk for low bone density after childhood cancer treatment.
authors: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.|Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors: Marissa A H
authors: MA
authors: den Hoed
authors: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.|Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors: Saskia M F
authors: SM
authors: Pluijm
authors: Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors: Lisette
authors: L
authors: Stolk
authors: Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors: André G
authors: AG
authors: Uitterlinden
authors: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors: Rob
authors: R
authors: Pieters
authors: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl.|Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands. m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl.
authors: Marry M
authors: MM
authors: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5
keywords: bone mineral density; endocrinology; epidemiology; genetic variation; late effects of cancer treatment; long-term survival; oncology; pediatric oncology; single-nucleotide polymorphisms