This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, J. A. Articles by Robison, L. L. Search for Related Content PubMed PubMed Citation Articles by Ross, J. A. Articles by Robison, L. L. Social Bookmarking                            What's this?

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

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
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.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
Improved treatments for childhood cancer during the last 30 years have dramatically increased long-term survival; 5-year relative survival rates of all childhood cancers combined increased from 56% during 1974 to 1976, to 77% during 1992 to 1998.¹ As a result of these advances in treatment, there is a large and growing number of childhood cancer survivors. Associated with this increased survival are long-term health-related consequences of therapy, including second malignancies, cardiovascular abnormalities, pulmonary complications, and obesity.² Because some of these adverse health effects may be modifiable, the identification of treatment and patient factors that contribute to them is important.

The Childhood Cancer Survivor Study (CCSS) is a cohort of more than 14,000 5-year survivors of childhood cancer from the United States and Canada who are being observed longitudinally to study late effects of cancer treatment.³ Oeffinger et al⁴ recently examined whether adult survivors of acute lymphoblastic leukemia (ALL) in the CCSS were at an increased risk for obesity and whether patient or treatment characteristics modified risk. A total of 1,765 survivors of childhood ALL were compared with 2,565 adult siblings of childhood cancer survivors. Using body mass index (BMI), the authors found that the age- and race-adjusted odds ratio (OR) for obesity (BMI 30) in survivors treated with cranial radiation therapy (CRT) 20 Gy in comparison with siblings was 2.59 (95% CI, 1.88 to 3.55) and 1.86 (95% CI, 1.33 to 2.57) for females and males, respectively. Female survivors were also more likely to be overweight (BMI = 25 to 29) in comparison with siblings. Furthermore, overweight or obesity was not associated with treatment consisting of chemotherapy only or radiation doses of less than 20 Gy.

One proposed mechanism to explain the association between CRT and obesity in survivors of childhood ALL is leptin insensitivity. Leptin is an adipocyte-derived hormone that binds to the biologically active long form of its receptor (LEPR) in the hypothalamus.⁵ It has been speculated that radiation-induced damage to the pituitary-hypothalamus axis may result in a disruption of leptin signal, which eventually results in obesity.⁶ Because the majority of patients treated for ALL do not develop this complication, it is possible that individual susceptibility through population polymorphism could contribute to adult survivors of childhood ALL becoming overweight or obese.

Polymorphisms in the LEPR gene have been studied with respect to obesity in healthy populations. Of these, Gln223Arg appears most consequential. Quinton et al⁷ found that postmenopausal women with the Arg allele had significantly lower leptin-binding affinity than women who were Gln homozygous, suggesting that this polymorphism affects ligand binding. Others have shown that carriers of the Arg allele have higher serum levels of leptin, and/or higher BMIs,^8-10 although the reports are not entirely consistent.^11,12 Given the diversity of populations studied and the polygenic nature of obesity, these contradictory results are not surprising. We hypothesized that the LEPR Gln223Arg polymorphism might influence susceptibility to obesity in childhood ALL survivors and that there may be an interaction with CRT.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
This study includes a subset of participants from the CCSS (a list of investigators appears in the Appendix). The current report is restricted to those individuals who met the following eligibility criteria: diagnosis and initial treatment for ALL at one of 25 collaborating CCSS institutions; diagnosis date between January 1, 1970, and December 31, 1986; age younger than 21 years at diagnosis; survived 5 years from diagnosis; participated in the Oeffinger et al⁴ analysis; and provided a buccal cell sample before the initiation of this study. The CCSS protocol and contact documents were reviewed and approved by the human subjects committee at each participating institution. Baseline data, including current weight and height without shoes, were collected for members of the study cohort in 1996 using a 24-page questionnaire.

Buccal Cell Collection
Buccal cell collection began in May 1999. Eligible patients were those who completed a baseline questionnaire for enrollment into the cohort, whose current address was known, who were alive at the date of the mailing of a request for a buccal cell sample, and who enrolled onto CCSS through an institution with institutional review board approval for collection and storage of buccal cell DNA (n = 21 institutions). CCSS participants (patients and sibling controls) were sent a specimen collection kit, which contained a cover letter describing the study, consent form, instruction sheet, a 45-mL bottle of mouthwash, specimen collection container, return mail labels, and postage. Subjects were instructed to rinse the mouth repeatedly with the mouthwash, and to return the used mouthwash to the laboratory in the sterile container. Informed written consent was obtained from all participants.

Genotyping
Genotyping was performed using the 5' nuclease allelic discrimination assay (TaqMan, Applied Biosystems, Foster City, CA). The genomic DNA sequence containing the region of interest in the LEPR gene (Gln223Arg) was analyzed using Primer Express software (Perkin-Elmer/Applied Biosystems Inc, Foster City, CA) to develop gene-specific polymerase chain reaction (PCR) primers and fluorogenic probes for allelic discrimination. The primer and probe oligonucleotide sequences to detect the polymorphisms were FP 5'-CAGCCAAACTCAACGACACTCT-3', RP 5'-TTACCCATATTTATGGGCTGAACTG-3'; VIC-A allele probe, ATTTTCCAGTCACCTCT; and FAM-G allele probe, AATTTTCCGGTCACCTC. Amplicons corresponding to the predicted size were identified by agarose gel electrophoresis (data not shown). Oligonucleotide template controls (common and variant) were produced (University of Minnesota Microchemical Facility, Minneapolis, MN). Each sequence contained one of the two possible allelic sequences present in the genome, encompassed by the binding sites for each primer. PCR cycling reactions were performed in duplicate in 96-well microtiter plates in a GeneAmp PCR System 9600 (Perkin-Elmer). Each reaction contained template DNA and a final concentration of 1x TaqMan PCR Master Mix (200 µmol/L each deoxynucleotide triphosphate, 1x potassium tris EDTA buffer [50 mmol/L KCl, 10 mmol/L Tris-HCl, 0.01 mmol/L EDTA], 60 nmol/L passive reference, 5 mmol/L MgCl₂, 0.01 u/µL AmpErase uracil-N-glycosylase, and 0.025u/µL AmpliTaq Gold), 300 nmol/L each TaqMan primer, 80 nmol/L wild-type FAM probe, and 150 nmol/L variant VIC probe. Thermocycling was performed with an initial 50°C incubation for 2 minutes followed by a 10-minute incubation at 95°C. A two-step cycling reaction was performed for 40 cycles with denaturation at 95°C for 15 seconds, and annealing and extension at 62°C for 1 minute. The reporter signal was normalized to the emission signal of the passive reference dye present in the TaqMan PCR Master Mix. Taking this value and subtracting the normalized value (no template controls) eliminates other fluctuations in the reaction and results in the Rn (change in normalized reporter) of the reaction. Allelic discrimination was determined by comparing the Rn values of the FAM-labeled probe to those of the VIC-labeled probe. Results were analyzed by the ABI TaqMan 7900 using sequence detection system 2.1 software (Applied Biosystems).

Analysis
The LEPR Gln223Arg was modeled using the Arg homozygous allele as the low-activity variant. On the basis of the analysis by Oeffinger et al,⁴ chemotherapy only and radiation treatment less than 20 Gy were combined and compared with radiation treatment 20 Gy, whereas overweight and obesity were combined and compared with BMI less than 25. The association between LEPR genotype and BMI (in kilograms per square meter), as well as potential interactions with CRT and age at diagnosis, were evaluated by the OR and corresponding 95% CIs using logistic regression.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
A total of 711 individuals included in the recent analysis by Oeffinger et al⁴ returned a buccal cell sample before the initiation of this laboratory study. Of these, 38 had missing race information and 54 were nonwhite or of Hispanic ethnicity. Because the frequency of the LEPR Gln223Arg polymorphism varies by race and ethnicity,¹³ we restricted our analyses to 619 non-Hispanic white ALL survivors with an available buccal cell sample. Six hundred (97%) samples were successfully amplified for the Gln223Arg genotype. The demographics and characteristics of these 600 ALL survivors who returned a buccal cell sample compared with the 891 non-Hispanic white ALL survivors who did not return a buccal cell sample are listed in Table 1. Although the mean age at baseline and the mean age at diagnosis were significantly different between the two groups, there were no statistically significant differences with respect to weight at baseline or treatment groups. The distribution of the Gln223Arg genotype among the ALL survivors was Gln/Gln (32%), Gln/Arg (48%), and Arg/Arg (20%), which was in Hardy-Weinberg equilibrium. This distribution is similar to literature reports,¹⁴ suggesting that the genotype is not associated with ALL.

View this table: [in this window] [in a new window]   Table 2. Prevalence for Being Normal Weight (BMI < 25 kg/m2), or Overweight or Obese (BMI 25 kg/m2) by Gln223Arg Genotype and Gender in White, Non-Hispanic Adult Survivors of Childhood ALL (N = 600)

View this table: [in this window] [in a new window]   Table 3. Sex-Specific ORs and 95% CIs for Being Overweight or Obese (BMI 25 kg/m2) by CRT and Age at Diagnosis in 600 Adult White, Non-Hispanic Survivors of Childhood ALL

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
Our study showed that the LEPR GlnQ223Arg polymorphism influenced susceptibility to obesity in female ALL survivors. Males had a similar distribution of the genotype regardless of weight. Studies of healthy children and adolescents show that serum leptin levels increase with age in girls but decrease in boys. Importantly, females have higher circulating levels of leptin compared with males, despite lower BMI, suggesting that females may be more resistant to the effects of leptin.¹⁵ In a study of 32 childhood ALL survivors and 35 age- and BMI-matched controls, leptin levels were highest in female survivors.⁶ Collectively, these data support a sex difference with respect to leptin regulation. Our data support the hypothesis that female ALL survivors who are homozygous for the Arg genotype have lower leptin binding affinity, as suggested by Quinton et al,⁷ although additional studies are needed.

The observation of an interaction between the homozygous Arg genotype and CRT is notable. It is possible that the Arg genotype in the presence of CRT may further decrease leptin receptor binding affinity in susceptible females. Although these results are preliminary, they may help explain why females seem most prone to obesity after CRT.

Several limitations of this study needed to be discussed. This study focused only on the leptin pathway for which CRT may influence obesity. Other pathways, including growth hormone deficiency,⁶ may also play a role. Height and weight were self-reported at one time point, which can lead to imprecision in calculating BMI. Measurement of self-reported height and weight, however, are generally accurate and do not contribute significantly to errors in assessing BMI.¹⁶ Moreover, BMI is the standard measure of obesity in most population-based studies. Our study was restricted to ALL survivors who were non-Hispanic white, thus the results might not be generalizable to other populations. Finally, because only 40% percent of ALL survivors in the recent analysis by Oeffinger et al⁴ had sent in a buccal cell sample before this analysis, it is possible that there are differences between the groups that may influence the results. However, we were able to compare the major variables of interest between the group of ALL survivors who returned a buccal cell sample with those who did not and found no statistically significant differences with BMI or radiation exposure.

Obesity in children and young adults is associated with an increased risk of developing cardiovascular disease, cancer, and diabetes in later life.^17,18 Importantly, recent modifications in treatment for children with ALL will likely reduce this late effect for future survivors. Nevertheless, many children with cancer still necessarily receive significant doses of CRT, which can influence future weight and height.^19,20 Additional study of LEPR polymorphisms is needed to confirm whether there is a sex effect and whether the Arg allele results in lower leptin receptor binding affinity. Identification of children at high risk of obesity after therapy might allow early targeted interventions to reduce subsequent obesity-related morbidity and mortality.

	Appendix

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
The following CCSS institutions and investigators participated in this study: University of California-San Francisco, CA (Arthur Ablin, MD*); University of Alabama, Birmingham, AL (Roger Berkow, MD*); International Epidemiology Institute, Rockville, MD (John Boice, Sc.D.); University of Washington, Seattle, WA (Norman Breslow, PhD); UT-Southwestern Medical Center at Dallas, TX (George R. Buchanan, MD*); Dana-Farber Cancer Institute, Boston, MA (Lisa Diller, MD,* Holcombe Grier, M.D, Frederick Li, MD); Texas Children's Center, Houston, TX (Zoann Dreyer, MD*); Children's Hospital and Medical Center, Seattle, WA (Debra Friedman, MD, MPH,* Thomas Pendergrass, MD); Roswell Park Cancer Institute, Buffalo, NY (Daniel M. Green, MD*); Hospital for Sick Children, Toronto, ON (Mark Greenberg, MB, ChB*); St Louis Children's Hospital, MO (Robert Hayashi, MD,* Teresa Vietti, MD); St Jude Children's Research Hospital, Memphis, TN (Melissa Hudson, MD*); University of Michigan, Ann Arbor, MI (Raymond Hutchinson, MD*); Stanford University School of Medicine, Stanford, CA (Michael P. Link, MD,* Sarah S. Donaldson, MD); Children's Hospital of Philadelphia, PA (Anna Meadows, MD,* Bobbie Bayton); Children's Hospital, Oklahoma City, OK (John Mulvihill, MD); Children's Hospital, Denver, CO (Brian Greffe,* Lorrie Odom, MD); Children's Health Care-Minneapolis, MN (Maura O'Leary, MD*); Columbus Children's Hospital, OH (Amanda Termuhlen, MD,* Frederick Ruymann, MD, Stephen Qualman, MD); Children's National Medical Center, Washington, DC (Gregory Reaman, MD,* Roger Packer, MD); Children's Hospital of Pittsburgh, PA (A. Kim Ritchey, MD,* Julie Blatt, MD); University of Minnesota, Minneapolis, MN (Leslie L. Robison, PhD,* Ann Mertens, PhD, Joseph Neglia, MD, MPH, Mark Nesbit, MD, Stella Davies, MD, PhD); Children's Hospital Los Angeles, CA (Kathy Ruccione, RN, MPH*); Memorial Sloan-Kettering Cancer Center New York (Charles Sklar, MD*); National Cancer Institute, Bethesda, MD (Malcolm Smith, MD, Martha Linet, MD); Mayo Clinic, Rochester, MN (W. Anthony Smithson, MD,* Gerald Gilchrist, MD); University of Texas M. D. Anderson Cancer Center, Houston, TX (Louise Strong, MD,* Marilyn Stovall, PhD); Riley Hospital for Children, Indianapolis, IN (Terry A. Vik, MD,* Robert Weetman, MD); Fred Hutchinson Cancer Center, Seattle, WA (Yutaka Yasui, PhD,* John Potter, MD, PhD); and University of California-Los Angeles, CA (Lonnie Zeltzer, MD*).

*Institutional principal investigator.

Former Institutional Principal Investigator.

Member CCSS Steering Committee.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	NOTES

 
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.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
1. Jemal A, Murray T, Samuels A, et al: Cancer statistics, 2003. CA Cancer J Clin 53:5-26, 2003[Abstract/Free Full Text]

2. Bhatia S, Landier W, Robison LL: Late effects of childhood cancer therapy, in DeVita VT, Hellman S, Rosenberg SA (ed): Progress in Oncology. Sudbury, MA, Jones and Bartlett, 2002, pp 171-201

3. Robison LL, Mertens AC, Boice JD, et al: Study design and cohort characteristics of the Childhood Cancer Survivor Study: A multi-institutional collaborative project. Med Pediatr Oncol 38:229-239, 2002[CrossRef][Medline]

4. Oeffinger KC, Mertens AC, Sklar CA, et al: Obesity in adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. J Clin Oncol 21:1359-1365, 2003[Abstract/Free Full Text]

5. Strosberg AD, Issad T: The involvement of leptin in humans revealed by mutations in leptin and leptin receptor genes. Trends Pharmacol Sci 20:227-230, 1999[CrossRef][Medline]

6. Brennan BM, Rahim A, Blum WF, et al: Hyperleptinaemia in young adults following cranial irradiation in childhood: Growth hormone deficiency or leptin insensitivity? Clin Endocrinol (Oxf) 50:163-169, 1999[CrossRef][Medline]

7. Quinton ND, Lee AJ, Ross RJ, et al: A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet 108:233-236, 2001[CrossRef][Medline]

8. van Rossum CT, Hoebee B, van Baak MA, et al: Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults. Obes Res 11:377-386, 2003[Medline]

9. Yiannakouris N, Yannakoulia M, Melistas L, et al: The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab 86:4434-4439, 2001[Abstract/Free Full Text]

10. Mattevi VS, Zembrzuski VM, Hutz MH: Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil. Int J Obes Relat Metab Disord 26:1179-1185, 2002[CrossRef][Medline]

11. Gotoda T, Manning BS, Goldstone AP, et al: Leptin receptor gene variation and obesity: Lack of association in a white British male population. Hum Mol Genet 6:869-876, 1997[Abstract/Free Full Text]

12. Rand L, Winchester EC, Millwood IY, et al: Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations. Int J Obes Relat Metab Disord 25:753-755, 2001[CrossRef][Medline]

13. Heo M, Leibel RL, Fontaine KR, et al: A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference. Int J Obes Relat Metab Disord 26:640-646, 2002[CrossRef][Medline]

14. Heo M, Leibel RL, Boyer BB, et al: Pooling analysis of genetic data: The association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity. Genetics 159:1163-1178, 2001[Abstract/Free Full Text]

15. Mantzoros CS: The role of leptin in human obesity and disease: A review of current evidence. Ann Intern Med 130:671-680, 1999[Abstract/Free Full Text]

16. Willett WC, Dietz WH, Colditz GA: Guidelines for healthy weight. N Engl J Med 341:427-434, 1999[Free Full Text]

17. Engeland A, Tretli S, Bjorge T: Height, body mass index, and ovarian cancer: A follow-up of 1.1 million Norwegian women. J Natl Cancer Inst 95:1244-1248, 2003[Abstract/Free Full Text]

18. Sinaiko AR, Donahue RP, Jacobs DR Jr, et al: Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults: The Minneapolis Children's Blood Pressure Study. Circulation 99:1471-1476, 1999[Abstract/Free Full Text]

19. Lustig RH, Post SR, Srivannaboon K, et al: Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 88:611-616, 2003[Abstract/Free Full Text]

20. Gurney JG, Ness KK, Stovall M, et al: Final height and body mass index among adult survivors of childhood brain cancer: Childhood cancer survivor study. J Clin Endocrinol Metab 88:4731-4739, 2003[Abstract/Free Full Text]

Submitted November 26, 2003; accepted June 4, 2004.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. C. Oeffinger, B. Adams-Huet, R. G. Victor, T. S. Church, P. G. Snell, A. L. Dunn, D. A. Eshelman-Kent, R. Ross, P. M. Janiszewski, A. J. Turoff, et al. Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia J. Clin. Oncol., August 1, 2009; 27(22): 3698 - 3704. [Abstract] [Full Text] [PDF]

				T. B. Haddy, R. B. Mosher, and G. H. Reaman Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia Clinical Pediatrics, July 1, 2009; 48(6): 601 - 608. [Abstract] [PDF]

				L. Diller, E. J. Chow, J. G. Gurney, M. M. Hudson, N. S. Kadin-Lottick, T. I. Kawashima, W. M. Leisenring, L. R. Meacham, A. C. Mertens, D. A. Mulrooney, et al. Chronic Disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings J. Clin. Oncol., May 10, 2009; 27(14): 2339 - 2355. [Full Text] [PDF]

				L. L. Robison, G. T. Armstrong, J. D. Boice, E. J. Chow, S. M. Davies, S. S. Donaldson, D. M. Green, S. Hammond, A. T. Meadows, A. C. Mertens, et al. The Childhood Cancer Survivor Study: A National Cancer Institute-Supported Resource for Outcome and Intervention Research J. Clin. Oncol., May 10, 2009; 27(14): 2308 - 2318. [Abstract] [Full Text] [PDF]

				E. G. Garmey, Q. Liu, C. A. Sklar, L. R. Meacham, A. C. Mertens, M. A. Stovall, Y. Yasui, L. L. Robison, and K. C. Oeffinger Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study J. Clin. Oncol., October 1, 2008; 26(28): 4639 - 4645. [Abstract] [Full Text] [PDF]

				G. T. Armstrong, C. A. Sklar, M. M. Hudson, and L. L. Robison Long-Term Health Status Among Survivors of Childhood Cancer: Does Sex Matter? J. Clin. Oncol., October 1, 2007; 25(28): 4477 - 4489. [Abstract] [Full Text] [PDF]

				R.-E. W. Kavey, V. Allada, S. R. Daniels, L. L. Hayman, B. W. McCrindle, J. W. Newburger, R. S. Parekh, and J. Steinberger Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics Circulation, December 12, 2006; 114(24): 2710 - 2738. [Abstract] [Full Text] [PDF]

				V. Paracchini, P. Pedotti, and E. Taioli Genetics of Leptin and Obesity: A HuGE Review Am. J. Epidemiol., July 15, 2005; 162(2): 101 - 114. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, J. A. Articles by Robison, L. L. Search for Related Content PubMed PubMed Citation Articles by Ross, J. A. Articles by Robison, L. L. Social Bookmarking                            What's this?