PURPOSE: 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. PATIENTS AND 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). CONCLUSION: CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.
PURPOSE: 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. PATIENTS AND 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). CONCLUSION:CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.
Authors: C A Fernandez; C Smith; W Yang; R Lorier; K R Crews; N Kornegay; J K Hicks; C F Stewart; J D Kawedia; L B Ramsey; C Liu; W E Evans; M V Relling; U Broeckel Journal: Clin Pharmacol Ther Date: 2012-08-08 Impact factor: 6.875
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Authors: H-W Park; S Tse; W Yang; H W Kelly; S C Kaste; C-H Pui; M V Relling; K G Tantisira Journal: Pharmacogenomics J Date: 2016-02-09 Impact factor: 3.550
Authors: Ching-Hon Pui; Jun J Yang; Stephen P Hunger; Rob Pieters; Martin Schrappe; Andrea Biondi; Ajay Vora; André Baruchel; Lewis B Silverman; Kjeld Schmiegelow; Gabriele Escherich; Keizo Horibe; Yves C M Benoit; Shai Izraeli; Allen Eng Juh Yeoh; Der-Cherng Liang; James R Downing; William E Evans; Mary V Relling; Charles G Mullighan Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544