Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.
OBJECTIVE
Overweight (body mass index [BMI] 25 to 29 kg/m2) and obesity (BMI > or = 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.


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 > or = 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 > or = 20 Gy cranial radiation, Arg/Arg individuals had six times higher odds of having BMI > or = 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.
Ross
Julie A
JA
Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. ross@epi.umn.edu
Oeffinger
Kevin C
KC
Davies
Stella M
SM
Mertens
Ann C
AC
Langer
Erica K
EK
Kiffmeyer
William R
WR
Sklar
Charles A
CA
Stovall
Marilyn
M
Yasui
Yutaka
Y
Robison
Leslie L
LL
D000293:Adolescent; D000328:Adult; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000532:radiotherapy / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D012737:Sex Factors
C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin