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Genetic variation and bone mineral density in long‐term adult survivors of childhood cancer
Author(s) -
den Hoed Marissa A. H.,
Pluijm Saskia M. F.,
Stolk Lisette,
Uitterlinden André G.,
Pieters Rob,
den HeuvelEibrink Marry M.
Publication year - 2016
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26198
Subject(s) - medicine , bone mineral , single nucleotide polymorphism , cohort , osteoporosis , minor allele frequency , calcitriol receptor , genotype , endocrinology , oncology , physiology , vitamin d and neurology , genetics , biology , gene
Purpose 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. Methods 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 (BMD TB ) and lumbar spine BMD (BMD LS ) 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 ). Results 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 BMD TB values (–1.16 vs. –0.82; P = 0.01) than those with the AG/AA genotype; however, BMD LS was not different. Carriers of two minor alleles (GG) of rs599083 ( LRP5 : low‐density lipoprotein receptor) revealed lower BMD TB (–1.20 vs. –0.78; P = 0.02) and lower BMD LS (–0.95 vs. –0.46; P = 0.01) values than those with the TT/TG genotype. Conclusion 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.