CRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia.
OBJECTIVE
Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits.


METHODS
The mean bone mineral density z scores of 309 long-term survivors of ALL were determined by quantitative computed tomography of the trabecular lumbar spine. We analyzed whether CRHR1 genotypes, adjusted for sex, ALL treatment regimen, and weight, could predict bone density.


RESULTS
We found that three single nucleotide polymorphisms (SNPs), all in linkage disequilibrium, were associated with bone density in a sex-specific manner. Bone density was lower in males (P = .001), in nonblack patients (P < .08), in those who were not overweight (P < .001), and in those who received intensive antimetabolites and glucocorticoids (P < .001). After adjustment for these features, the G allele at the rs1876828 SNP was associated with lower z scores (P = .02) in males but tended to have the opposite association in females (P = .09).


CONCLUSIONS
CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.
Jones
Terreia S
TS
Department of Radiology, Colleges of Pharmacy and Medicine, University of Tennessee, Memphis, TN, USA.
Kaste
Sue C
SC
Liu
Wei
W
Cheng
Cheng
C
Yang
Wenjian
W
Tantisira
Kelan G
KG
Pui
Ching-Hon
CH
Relling
Mary V
MV
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D015519:Bone Density / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D017741:Survivors; D000099052:CRF Receptor, Type 1
D000305:Adrenal Cortex Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1