TY - JOUR
T1 - Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia
T2 - A report from the childhood cancer survivor study
AU - Ross, Julie A.
AU - Oeffinger, Kevin C.
AU - Davies, Stella M.
AU - Mertens, Ann C.
AU - Langer, Erica K.
AU - Kiffmeyer, William R.
AU - Sklar, Charles A.
AU - Stovall, Marilyn
AU - Yasui, Yutaka
AU - Robison, Leslie L.
PY - 2004
Y1 - 2004
N2 - Purpose: Overweight (body mass index [BMI] 25 to 29 kg/m2) and obesity (BMI ≥ 30 kg/m2) frequently follow treatment for childhood acute lymphoblastic leukemia (ALL). Recent studies suggest that risk is most apparent in females treated with cranial radiation at a younger age. Because radiation at a young age may affect the hypothalamus causing leptin receptor insensitivity, we hypothesized that a polymorphism in the leptin receptor (LEPR) gene, Gln223Arg, might influence susceptibility to obesity in survivors of childhood ALL. Patients and Methods: We genotyped 600 non-Hispanic white adult ALL survivors enrolled onto the Childhood Cancer Survivor Study. BMI was compared between those with two copies of the Arg allele to those who had at least one copy of the Gln allele. Results: Female survivors with BMI ≥ 25 kg/m2 were more likely Arg homozygous than those with BMI less than 25 kg/m2 (24% v 12%; P = .007). This difference was not observed in males. Moreover, among females treated with ≥ 20 Gy cranial radiation, Arg/Arg individuals had six times higher odds of having BMI ≥ 25 kg/m 2 (95% CI, 2.1 to 22.0) than those with a Gln allele (P = .04 for interaction). Conclusion: LEPR polymorphism may influence obesity in female survivors of childhood ALL, particularly those exposed to cranial radiation. Because obesity is associated with increased morbidity and mortality in later life, identification of children at high risk might allow for early targeted interventions.
AB - Purpose: Overweight (body mass index [BMI] 25 to 29 kg/m2) and obesity (BMI ≥ 30 kg/m2) frequently follow treatment for childhood acute lymphoblastic leukemia (ALL). Recent studies suggest that risk is most apparent in females treated with cranial radiation at a younger age. Because radiation at a young age may affect the hypothalamus causing leptin receptor insensitivity, we hypothesized that a polymorphism in the leptin receptor (LEPR) gene, Gln223Arg, might influence susceptibility to obesity in survivors of childhood ALL. Patients and Methods: We genotyped 600 non-Hispanic white adult ALL survivors enrolled onto the Childhood Cancer Survivor Study. BMI was compared between those with two copies of the Arg allele to those who had at least one copy of the Gln allele. Results: Female survivors with BMI ≥ 25 kg/m2 were more likely Arg homozygous than those with BMI less than 25 kg/m2 (24% v 12%; P = .007). This difference was not observed in males. Moreover, among females treated with ≥ 20 Gy cranial radiation, Arg/Arg individuals had six times higher odds of having BMI ≥ 25 kg/m 2 (95% CI, 2.1 to 22.0) than those with a Gln allele (P = .04 for interaction). Conclusion: LEPR polymorphism may influence obesity in female survivors of childhood ALL, particularly those exposed to cranial radiation. Because obesity is associated with increased morbidity and mortality in later life, identification of children at high risk might allow for early targeted interventions.
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U2 - 10.1200/JCO.2004.11.152
DO - 10.1200/JCO.2004.11.152
M3 - Article
C2 - 15337805
AN - SCOPUS:4444346898
SN - 0732-183X
VL - 22
SP - 3558
EP - 3562
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -