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Genetic Variation in the Leptin Receptor Gene and Obesity in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study

From the Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN; Department of Family Practice and Community Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas; Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, TX; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Pediatric Hematology Oncology; Memorial Sloan-Kettering Cancer Center, New York, NY; and Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA

Address reprint requests to Julie A. Ross, PhD, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota Cancer Center, 420 Delaware St SE, MMC 422, Minneapolis, MN 55455; e-mail: ross{at}epi.umn.edu

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/m² (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.

Supported by grants from the National Cancer Institute (U24 CA-55727), Bethesda, MD, and the Children's Cancer Research Fund, Minneapolis, MN.

Presented at the American Society of Hematology Meeting, San Diego, CA, December 6-9, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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