Cancer Causes & Control

, 22:899 | Cite as

Height at diagnosis and birth-weight as risk factors for osteosarcoma

  • Lisa MirabelloEmail author
  • Ruth Pfeiffer
  • Gwen Murphy
  • Najat C. Daw
  • Ana Patiño-Garcia
  • Rebecca J. Troisi
  • Robert N. Hoover
  • Chester Douglass
  • Joachim Schüz
  • Alan W. Craft
  • Sharon A. Savage
Original paper



Osteosarcoma typically occurs during puberty. Studies of the association between height and/or birth-weight and osteosarcoma are conflicting. Therefore, we conducted a large pooled analysis of height and birth-weight in osteosarcoma.


Patient data from seven studies of height and three of birth-weight were obtained, resulting in 1,067 cases with height and 434 cases with birth-weight data. We compared cases to the 2000 US National Center for Health Statistics Growth Charts by simulating 1,000 age- and gender-matched controls per case. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between height or birth-weight and risk of osteosarcoma for each study were estimated using logistic regression. All of the case data were combined for an aggregate analysis.


Compared to average birth-weight subjects (2,665–4,045 g), individuals with high birth-weight (≥4,046 g) had an increased osteosarcoma risk (OR 1.35, 95% CI 1.01–1.79). Taller than average (51st–89th percentile) and very tall individuals (≥90th percentile) had an increased risk of osteosarcoma (OR 1.35, 95% CI 1.18–1.54 and OR 2.60, 95% CI 2.19–3.07, respectively; P trend < 0.0001).


This is the largest analysis of height at diagnosis and birth-weight in relation to osteosarcoma. It suggests that rapid bone growth during puberty and in utero contributes to OS etiology.


Osteosarcoma Height Birth-weight Meta-analysis Epidemiology 



This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Center for Cancer Research.

Supplementary material

10552_2011_9763_MOESM1_ESM.doc (639 kb)
Supplementary material 1 (DOC 639 kb)


  1. 1.
    Mascarenhas L, Siegel S, Spector L, Arndt C, Femino D, Malogolowkin M (2006) Malignant bone tumors: cancer in 15- to 29-year-olds in the United States. In: Bleyer AOLM, Barr R, Ries LAG (eds) Cancer epidemiology in older adolescents and young adults 15 to 29 years of age, including SEER incidence and survival: 1975–2000. National Cancer Institute, Bethesda NIH Pub. No. 06-5767, pp 98–109Google Scholar
  2. 2.
    Dahlin DC, Unni KK (1986) Bone Tumors: general aspects and data on 8, 542 cases, 4th ed edn. Thomas, SpringfieldGoogle Scholar
  3. 3.
    Dorfman HA, Czerniak B (1995) Bone cancers. Cancer Suppl 75:203–210Google Scholar
  4. 4.
    Fuchs B, Pritchard DJ (2002) Etiology of osteosarcoma. Clin Orthop Relat Res 397:40–52PubMedCrossRefGoogle Scholar
  5. 5.
    Hanson MF, Seton M, Merchant A (2006) Osteosarcoma in Paget’s disease of bone. J Bone Miner Res 21:P58–P63CrossRefGoogle Scholar
  6. 6.
    Varley JM (2003) Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 21:313–320PubMedCrossRefGoogle Scholar
  7. 7.
    Chauveinc L, Mosseri V, Quintana E et al (2001) Osteosarcoma following retinoblastoma: age at onset and latency period. Ophthalmic Genet 22:77–88PubMedCrossRefGoogle Scholar
  8. 8.
    Lipton JM, Federman N, Khabbaze Y et al (2001) Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry. J Pediatr Hematol Oncol 23:39–44PubMedCrossRefGoogle Scholar
  9. 9.
    Wang LL, Gannavarapu A, Kozinetz CA et al (2003) Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 95:669–674PubMedCrossRefGoogle Scholar
  10. 10.
    Mirabello L, Troisi RJ, Savage S (2009) Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115:1531–1543PubMedCrossRefGoogle Scholar
  11. 11.
    Unni KK (1996) Dahlin’s bone tumors: general aspects and data on 11,087 cases. In. 5 edn. Philadelphia: Lippincott-Raven, pp 143–183Google Scholar
  12. 12.
    Dorfman HA, Czerniak B (1997) Bone tumors. St. Louis, Mosby, pp 128–252Google Scholar
  13. 13.
    Glass AG, Fraumeni JF (1970) Epidemiology of bone cancer in children. J Natl Cancer Inst 44:187–199PubMedGoogle Scholar
  14. 14.
    Miller RW (1981) Contrasting epidemiology of childhood osteosarcoma, Ewing’s sarcoma, and rhabdomyosarcoma. Nat Cancer Inst Monogr 56:9–15PubMedGoogle Scholar
  15. 15.
    Withrow SJ, Powers BE, Straw RC, RM Wilkins (1991) Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop Relat Res 270:159–168PubMedGoogle Scholar
  16. 16.
    Tjalma RA (1966) Canine bone sarcoma: estimation of relative risk as a function of body size. J Natl Cancer Inst 36:1137–1150PubMedGoogle Scholar
  17. 17.
    Fraumeni JF Jr (1967) Stature and malignant tumors of the bone in childhood and adolescence. Cancer 20:967–973PubMedCrossRefGoogle Scholar
  18. 18.
    Troisi R, Masters MN, Joshipura K et al (2006) Perinatal factors, growth and development, and osteosarcoma risk. Br J Cancer 95:1603–1607PubMedCrossRefGoogle Scholar
  19. 19.
    Scranton PE, DeCicco FA, Totten RS, Yunis EJ (1975) Prognostic factors in osteosarcoma. A review of 20 years’ experience at the University of Pittsburgh Health Center Hospitals. Cancer 36:2179–2191PubMedCrossRefGoogle Scholar
  20. 20.
    Gelberg KH, Fitzgerald E, Hwang S, Dubrow R (1997) Growth and development and other risk factors for osteosarcoma in children and young adults. Int J Epidemiol 26:272–278PubMedCrossRefGoogle Scholar
  21. 21.
    Rytting M, Pearson P, Raymond AK et al (2000) Osteosarcoma in preadolescent patients. Clin Orthop Relat Res 373:39–50PubMedCrossRefGoogle Scholar
  22. 22.
    Ruza E, Sotillo E, Sierrasesúmaga L, Azcona C, Patiño-Garcia A (2003) Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Iα1 genes and their relationship with height in children with bone cancer. J Pediatr Hematol Oncol 25:780–786PubMedCrossRefGoogle Scholar
  23. 23.
    Cotterill SJ, Wright CM, Pearce MS, Craft AW (2004) Stature of young people with malignant bone tumors. Pediatr Blood Cancer 42:59–63PubMedCrossRefGoogle Scholar
  24. 24.
    Longhi A, Pasini A, Cicognami A et al (2005) Height as a risk factor for osteosarcoma. J Pediatr Hematol Oncol 27:314–318PubMedCrossRefGoogle Scholar
  25. 25.
    Goodman MA, McMaster JH, Drash AL et al (1978) Metabolic and endocrine alterations in osteosarcoma patients. Cancer 42:603–610PubMedCrossRefGoogle Scholar
  26. 26.
    Broström LA, Adamson U, Filipsson R, Hall K (1979) Longitudinal growth and dental development in osteosarcoma patients. Acta Orthop Scand 51:755–759Google Scholar
  27. 27.
    Vassilopoulou-Sellin R, Wallis CJ, Samaan NA (1985) Hormonal evaluation in patients with osteosarcoma. J Surg Oncol 28:209–213PubMedCrossRefGoogle Scholar
  28. 28.
    Operskalski EA, Preston-Martin S, Henderson BE, Visscher BR (1987) A case-control study of osteosarcoma in young persons. Am J Epidemiol 126:118–126PubMedGoogle Scholar
  29. 29.
    Pui CH, Dodge RK, George SL, Green AA (1987) Height at diagnosis of malignancies. Arch Dis Child 62:495–499PubMedCrossRefGoogle Scholar
  30. 30.
    Glasser DB, Duane K, Lane JM, Healey JH, Caparros-Sison B (1991) The effect of chemotherapy on growth in the skeletally immature individual. Clin Orthop Relat Res 262:93–100PubMedGoogle Scholar
  31. 31.
    Buckley JD, Pendergrass TW, Buckley CM et al (1998) Epidemiology of osteosarcoma and Ewing’s sarcoma in children: a study of 305 cases by the Children’s Cancer Group. Cancer 83:1440–1448PubMedCrossRefGoogle Scholar
  32. 32.
    Cool WP, Grimer RJ, Carter SR, Tillman RM, Davies AM (1998) Longitudinal growth following treatment for osteosarcoma. Sarcoma 2:115–119PubMedCrossRefGoogle Scholar
  33. 33.
    Hartley AL, Birch JM, McKinney PA et al (1988) The inter-regional epidemiological study of childhood cancer (IRESCC): case control study of children with bone and soft tissue sarcomas. Br J Cancer 58:838–842PubMedCrossRefGoogle Scholar
  34. 34.
    Schüz J, Forman MR (2007) Birthweight by gestational age and childhood cancer. Cancer Causes Control 18:655–663PubMedCrossRefGoogle Scholar
  35. 35.
    Schuz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J (1999) Association of childhood cancer with factors related to pregnancy and birth. Int J Epidemiol 28:631–639PubMedCrossRefGoogle Scholar
  36. 36.
    Kuczmarski RJ, Ogden CL, Guo SS et al (2002) 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11:1–190Google Scholar
  37. 37.
    Hernández M, Castellet J, Narvaiza JL et al (1988) Curvas y tablas de crecimiento. Instituto de investigación sobre crecimiento y desarrollo. Orbegozo Editorial Garsi, Fundación F. MadridGoogle Scholar
  38. 38.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  39. 39.
    Higgins JP (2008) Commentary: heterogeneity in meta-analysis should be expected and appropriately quantified. Int J Epidemiol 37:1158–1160PubMedCrossRefGoogle Scholar
  40. 40.
    Egger M, Davey-Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634Google Scholar
  41. 41.
    Begg CB, Mazumdar M (1994) Operating characteristics of rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRefGoogle Scholar
  42. 42.
    Hjalgrim LL, Westergaard T, Rostgaard K et al (2003) Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 158:724–735PubMedCrossRefGoogle Scholar
  43. 43.
    Harder T, Plagemann A, Harder A (2008) Birth weight and subsequent risk of childhood primary brain tumors: a meta-analysis. Am J Epidemiol 168:366–373PubMedCrossRefGoogle Scholar
  44. 44.
    Harder T, Plagemann A, Harder A (2010) Birth weight and risk of neuroblastoma: a meta-analysis. Int J Epidemiol 39:746–756PubMedCrossRefGoogle Scholar
  45. 45.
    Ognjanovic S, Carozza SE, Chow EJ et al. (2009) Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype. Br J Cancer Dec 8. [Epub ahead of print]Google Scholar
  46. 46.
    Leisenring WM, Breslow NE, Evans IE et al (1994) Increased birth weights of National Wilms’ Tumor Study patients suggest a growth factor excess. Cancer Res 54:4680–4683PubMedGoogle Scholar
  47. 47.
    Schüz J, Schmidt LS, Kogner P et al. (2010) Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study. Int J Cancer [Epub ahead of print]Google Scholar
  48. 48.
    Smith A, Lightfoot T, Simpson J, Roman E, UKCCS investigators (2009) Birth weight, sex and childhood cancer: a report from the United Kingdom Childhood Cancer Study. Cancer Epidemiol Biomarkers Prev 33:363–367Google Scholar
  49. 49.
    Crowther NJ, Hiller JE, Moss JR et al (2005) Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352:2477–2486PubMedCrossRefGoogle Scholar
  50. 50.
    Ross JA, Perentesis JP, Robison LL, Davies SM (1996) Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7:553–559PubMedCrossRefGoogle Scholar
  51. 51.
    Murphy VE, Smith R, Giles WB, Clifton VL (2006) Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr Rev 27:141–169PubMedCrossRefGoogle Scholar
  52. 52.
    Furstenberger G, Senn HJ (2002) Insulin-like growth factors and cancer. Lancet Oncol 3:298–302PubMedCrossRefGoogle Scholar
  53. 53.
    Lagiou P, Hsieh CC, Lipworth L et al (2009) Insulin-like growth factor levels in cord blood, birth weight and breast cancer risk. Br J Cancer 100:1794–1798PubMedCrossRefGoogle Scholar
  54. 54.
    Raqib R, Alam DS, Sarker P et al (2007) Low birth weight is associated with altered immune function in rural Bangladeshi children: a birth cohort study. Am J Clin Nutr 85:845–852PubMedGoogle Scholar
  55. 55.
    Charalambous M, da Rocha ST, Ferguson-Smith AC (2007) Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Curr Opin Endocrinol Diabetes Obes 14:3–12PubMedCrossRefGoogle Scholar
  56. 56.
    Michels KB, Xue F (2006) Role of birth weight in the etiology of breast cancer. Int J Cancer 119:2007–2025PubMedCrossRefGoogle Scholar
  57. 57.
    Eriksson M, Wedel H, Wallander MA et al (2007) The impact of birth weight on prostate cancer incidence and mortality in a population-based study of men born in 1913 and followed up from 50 to 85 years of age. Prostate 67:1247–1254PubMedCrossRefGoogle Scholar
  58. 58.
    Cnattingius S, Lundberg F, Sandin S, Grönberg H, Iliadou A (2009) Birth characteristics and risk of prostate cancer: the contribution of genetic factors. Cancer Epidemiol Biomarkers Prev 18:2422–2426PubMedCrossRefGoogle Scholar
  59. 59.
    Tanner JM, Whitehouse RH, Takaishi M (1966) Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. Part I. Arch Dis Child 41:454–471PubMedCrossRefGoogle Scholar
  60. 60.
    Larsson SE, Lorentzon R (1974) The incidence of malignant primary bone tumours in relation to age, sex and site—a study of osteogenic sarcoma, chondrosarcoma and Ewing’s sarcoma diagnosed in Sweden from 1958 to 1968. J Bone Joint Surg 56-B:534–540Google Scholar
  61. 61.
    Price CHG (1958) Primary bone-forming tumours and their relationship to skeletal growth. J Bone Joint Surg 408:574–593Google Scholar
  62. 62.
    Fraumeni JF Jr, Boice JD (1982) Bone. In: DFJJ Schottenfeld (ed) Cancer epidemiology and prevention. W B Saunders Co, PhiladelphiaGoogle Scholar
  63. 63.
    Mirabello L, Troisi RJ, Savage SA (2009) International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 125:229–234PubMedCrossRefGoogle Scholar
  64. 64.
    Ru G, Terracini B, Glickman LT (1998) Host related risk factors for canine osteosarcoma. Vet J 156:31–39PubMedCrossRefGoogle Scholar
  65. 65.
    Ruddon RW (1987) Cancer biology. Oxford University Press, New YorkGoogle Scholar
  66. 66.
    Savage SA, Woodson K, Walk E et al (2007) Analysis of genes critical for growth regulation identifies Insulin-like Growth Factor 2 Receptor variations with possible functional significance as risk factors for osteosarcoma. Cancer Epidemiol Biomarkers Prev 16:1667–1674PubMedCrossRefGoogle Scholar
  67. 67.
    Kappel CC, Velez-Yanguas MC, Hirschfeld S, Helman LJ (1994) Human osteosarcoma cell lines are dependent on insulin-like growth factor I for in vitro growth. Cancer Res 54:2803–2807PubMedGoogle Scholar
  68. 68.
    Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4:505–518PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. (outside the USA) 2011

Authors and Affiliations

  • Lisa Mirabello
    • 1
    • 9
    Email author
  • Ruth Pfeiffer
    • 1
  • Gwen Murphy
    • 1
  • Najat C. Daw
    • 2
  • Ana Patiño-Garcia
    • 3
  • Rebecca J. Troisi
    • 1
    • 4
  • Robert N. Hoover
    • 1
  • Chester Douglass
    • 5
  • Joachim Schüz
    • 6
    • 7
  • Alan W. Craft
    • 8
  • Sharon A. Savage
    • 1
  1. 1.Department of Health and Human Services, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Department of Oncology, St Jude Children’s Research Hospital, and Department of PediatricsUniversity of Tennessee, College of MedicineMemphisUSA
  3. 3.Department of PediatricsLaboratory of Pediatrics, Pediatric Oncology UnitUniversity Clinic of NavarraPamplonaSpain
  4. 4.Department of Community and Family MedicineDartmouth Medical SchoolLebanonUSA
  5. 5.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  6. 6.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  7. 7.Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University of MainzMainzGermany
  8. 8.Department of Child HealthUniversity of Newcastle upon TyneNewcastle upon TyneUK
  9. 9.Clinical Genetics Branch, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIHRockvilleUSA

Personalised recommendations