Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study Journal Article
| Authors: | Ross, J. A.; Oeffinger, K. C.; Davies, S. M.; Mertens, A. C.; Langer, E. K.; Kiffmeyer, W. R.; Sklar, C. A.; Stovall, M.; Yasui, Y.; Robison, L. L. |
| Article Title: | Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study |
| Abstract: | 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. © 2004 by American Society of Clinical Oncology. |
| Keywords: | adolescent; adult; cancer survival; child; controlled study; human cell; major clinical study; genetics; brain radiation; allele; genetic variability; genotype; obesity; acute lymphoblastic leukemia; skull irradiation; cranial irradiation; homozygosity; body mass; sex difference; acute lymphocytic leukemia; sex factors; childhood leukemia; dna polymorphism; cell surface receptor; receptors, cell surface; cheek; leptin receptor; gamma radiation; variation (genetics); leukemia, lymphocytic, acute, l1; humans; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 22 |
| Issue: | 17 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2004-09-01 |
| Start Page: | 3558 |
| End Page: | 3562 |
| Language: | English |
| DOI: | 10.1200/jco.2004.11.152 |
| PROVIDER: | scopus |
| PUBMED: | 15337805 |
| DOI/URL: | |
| Notes: | J. Clin. Oncol. -- Cited By (since 1996):70 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work