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Vol. 63. Núm. 6.
Páginas 537-547 (Diciembre 2005)
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Vol. 63. Núm. 6.
Páginas 537-547 (Diciembre 2005)
Artículo especial
DOI: 10.1016/S1695-4033(05)70254-X
Acceso a texto completo
Factores de riesgo para los tumores óseos malignos pediátricos
Risk factors for pediatric malignant bone tumors
Visitas
...
J. Ferrís i Tortajadaa,b,??
Autor para correspondencia
ferris_jos@gva.es
http://www.pehsu.org

Correspondencia: Dr. J. Ferrís i Tortajada. Unidad de Salud Medioambiental. Sección de Oncología Pediátrica. Hospital Universitario Materno-Infantil La Fe. Avda. Campanar, 21. 46009 Valencia. España.
, O. Berbel Torneroa, J.A. Ortega Garcíaa, L. Claudio-Moralesd, J. García i Castelle, V. Martí Peralesf, L. Miranda Casasf
a Unidad de Salud Medioambiental Pediátrica. Hospital Universitario Virgen de la Arrixaca. Murcia. España
b Sección de Oncología Pediátrica. Hospital Materno-Infantil Universitario La Fe. Valencia. Unidad de Salud Medicoambiental Pediátrica. Hospital Universitario Virgen de la Arrixaca. Murcia. España
d Department of Community and Preventive Medicine. Mount Sinai School of Medicine. Nueva York. EE.UU. España
e Servicio de Anatomía Patológica. Hospital de Sagunto. Valencia. España
f Sección de Traumatología y Ortopedia Pediátrica. Hospital Materno-Infantil Universitario La Fe. Valencia. España
Información del artículo
Introducción

El cáncer es el resultado final de la interacción multifactorial de dos clases de determinantes, el genético (endógeno) y el ambiental (exógeno). El progreso evidenciado por la oncología pediátrica, durante las últimas décadas, también se ha reflejado en los tumores óseos malignos (TOM). Estos avances se centran en los aspectos diagnósticos y terapéuticos, pero no en los factores de riesgo (FR) implicados en su etiopatogenia.

Objetivo

La presente revisión tiene tres objetivos: a) actualizar el conocimiento de los FR asociados con los TOM durante la época pediátrica y adulta; b) divulgar entre todos nuestros compañeros los principales FR relacionados a los TOM, para fomentar su investigación, diagnóstico y futura prevención, y c) solicitar la ayuda de nuestros colegas para el proyecto de investigación Medio ambiente y cáncer pediátrico.

Material y métodos

Revisión bibliográfica sistemática, de los últimos 30 años, de los FR implicados en la etiopatogenia de los TOM, obtenida del Medline, Cancerlit, Index Citation Science y Embase. Los perfiles de búsqueda utilizados han sido: pediatric/ childhood malignant bone tumors, pediatric/childhood bone cancer/neoplasm, osteosarcoma/bone sarcoma/ Ewing's sarcoma and risk factors/etiology/epidemiology. Se han seleccionado los artículos más interesantes y de sus referencias, las más relevantes.

Resultados

Los TOM constituyen el 6-7% de los cánceres pediátricos. Las dos variedades más frecuentes son el osteosarcoma (OTS) y el sarcoma de Ewing (SE), con el 56 y el 34% de los casos, respectivamente. Los FR asociados con el OTS son los siguientes: a) patologías óseas preexistentes (enfermedad de Paget); b) factores genético-familiares (retinoblastoma hereditario, síndrome de Li-Fraumeni, syndrome de Rothmund-Thompson, síndrome de Bloom, OTS familiar y anemia de Diamond-Blackfan); c) factores químicos (sustancias antineoplásicas); d) factores físicos (radiación ionizante); e) factores biológicos; f) ocupaciones parentales, y g) otros factores (implantes óseos artificiales y traumatismos). Los FR asociados con el SE son los siguientes: a) étnico-culturales (raza blanca); b) factores genéticos; c) ocupaciones parentales (exposiciones laborables a herbicidas, pesticidas y fertilizantes); d) antecedents obstétricos maternos, y e) otros factores (tabaquismo parental y hernias inguinales).

Conclusiones

La mayoría de las causas de los TOM son desconocidas. Los principales FR implicados, con mayor o menor evidencia científica, en la etiopatogenia del OTS son: enfermedad de Paget, retinoblastoma hereditario, síndrome de Li-Fraumeni, sustancias antineoplásicas y radiación ionizante. Los principales FR asociados al SE son: raza blanca, exposiciones ocupacionales parentales, tabaquismo parental y antecedente de hernia inguinal intervenida. Las principales dificultades para avanzar en el conocimiento de los FR relacionados con el desarrollo de los TOM son: a) su origen multifactorial; b) la baja prevalencia poblacional; c) la inexistente formación en salud medioambiental pediátrica, y d) los escasos presupuestos económicos públicos o privados destinados a tal finalidad.

Palabras clave:
Tumores óseos malignos pediátricos
Osteosarcoma
Sarcoma de Ewing
Factores de riesgo
Introduction

Cancer is the result of the interaction of two kinds of determinants: genetic (endogenous) and environmental (exogenous). In the last few decades, pediatric oncology as a whole has progressed, including knowledge of malignant osseous tumors (MOT). Although advances have been made in diagnostic and therapeutic aspects, little progress has taken place in our knowledge of the risk factors involved in their etiopathogenesis.

Objective

This review has three objectives: a) to provide an update on MOT-related risk factors in the child and adult population; b) to disseminate knowledge of the main MOT-related risk factors among our colleagues in order to promote research into these factors, diagnosis and future prevention, and c) to request help from our colleagues in the Environment and Pediatric Cancer research project.

Material and methods

We performed a systematic review of the literature published in the last 30 years on risk factors implicated in the etiopathogenesis of MOT, using Medline, Cancerlit, Science Citation Index and Embase. The search profiles used were: pediatric/childhood malignant bone tumors, pediatric/ childhood bone cancer/neoplasm, osteosarcoma/bone sarcoma/Ewing's sarcoma and risk factors/etiology/epidemiology. The most interesting articles were selected and the most relevant references contained therein were retrieved.

Results

MOT represent 6-7% of all pediatric neoplasms. The most frequent types are osteosarcoma (OS) and Ewing's sarcoma (ES), representing 56 % and 34 % respectively. OS-related risk factors are the following: a) previous osseous disease (Paget's disease); b) familial-genetic factors (hereditary retinoblastoma, Li-Fraumeni syndrome, Rothmund- Thompson syndrome, Bloom syndrome, familial OS, Diamond-Blackfan anemia); c) chemical factors (antineoplastic drugs); d) physical factors (ionizing radiation); e) biologic factors; f) parental occupation, and g) other factors (artificial osseous implants and traumatisms). ES-related risk factors are the following: a) ethnic-cultural (Caucasian race); b) genetic factors; c) parental occupation (herbicide, pesticide ad fertilizer exposure); d) maternal obstetric history, and e) other factors (parental smoking and inguinal hernia).

Conclusions

Most causes of MOT are unknown. Based on different levels of scientific evidence, the main factors implicated in the etiopathogenesis of OS are: Paget's disease, hereditary retinoblastoma, Li-Fraumeni syndrome, antineoplastic drugs, and ionizing radiation. The main factors related to ES are: Caucasian race, parental occupation, parental smoking, and surgery for inguinal hernia. The main obstacles to greater knowledge of MOT-related factors are: a) their multiple origin; b) the low prevalence in the population; c) lack of environmental health training in pediatrics, and d) the low public and private investment in this research field.

Key words:
Pediatric malignant bone tumour
Osteosarcoma
Ewing's sarcoma
Risk factor
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Bibliografía
[1.]
M.M. Malawer, M.P. Link, S.S. Donaldson.
Sarcomas of bone.
Cancer principles and practice of oncology, 6th ed., pp. 1891-1935
[2.]
Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, et al, editors. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. National Cancer Institute. SEER Program. NIH Pub No 99-4649. Bethesda, MD, 1999.
[3.]
A. Muñoz Villa.
Tumores óseos malignos.
Hematología y oncología pediátricas, 1.ª ed., pp. 557-572
[4.]
Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International Classification of Childhood Cancer. 3rd ed. Cancer. 2005; 103:1457-67.
[5.]
K.M. Yaw.
Pediatric bone tumors.
Semin Surg Oncol, 16 (1999), pp. 173-183
[6.]
M.P. Link, M.C. Gebhart, P.A. Meyers.
Osteosarcoma.
Principles and practice of pediatric oncology, 4th ed., pp. 1051-1089
[7.]
J.P. Ginsberg, S.Y. Woo, M.E. Johson, M.J. Hicks, M.E. Horowitz.
Ewing's Sarcoma Family of Tumors: Ewing's Sarcoma of Bone and Soft Tissue and the Peripheral Primitive Neuroectodermal Tumors.
Principles and practice of pediatric oncology, 4th ed., pp. 973-1016
[8.]
R.W. Miller, J.D. Boice, R.E. Curtis.
Bone Cancer..
Cancer Epidemiology and Prevention, 2nd ed., pp. 971-983
[9.]
M.F. Hansen, M.J. Nelissery, P. Bhatia.
Common mechanisms of osteosarcoma and Paget's disease.
J Bone Miner Res, 14 (1999), pp. 39-44
[10.]
J.D. McNairn, T.A. Damron, S.K. Landas, J.L. Ambrose, A.E. Shrimpton.
Inheritance of osteosarcoma and Paget's disease of bone: A familial loss of heterozygosity study.
J Mol Diagn, 3 (2001), pp. 171-177
[11.]
B. Fuchs, D.J. Pritchard.
Etiology of osteosarcoma.
Clin Orthopaed Related Res, 397 (2002), pp. 40-52
[12.]
F.P. Li.
Familial Aggregation.
Cancer epidemiology and prevention, 2nd ed., pp. 546-558
[13.]
N.M. Lindor, M.H. Greene, and the Mayo Familial Cancer Program.
The concise handbook of family cancer syndromes.
J Natl Cancer Inst, 90 (1998), pp. 1039-1071
[14.]
L. Sierrasesúmaga, A. Patiño.
Retinoblastoma.
Hematología y oncología pediátricas, pp. 573-582
[15.]
R.L. Hurwitz, C.L. Shields, J.A. Shields, P. Chávez-Barrios, M.Y. Hurwitz, M.M. Chintagumpala.
Retinoblastoma.
Principles and practice of pediatric oncology, 4th ed., pp. 825-846
[16.]
J. Ferrís i Tortajada, J. Garcia i Castell, J.A. López Andreu, C. Pellicer Porres.
Factores genéticos asociados a cánceres pediátricos.
An Esp Pediatr, 30 (1999), pp. 4-13
[17.]
J.M. El-Khoury, S.N. Hadad, N.G. Atallah.
Osteosarcomatosis with Rothmund-Thompson syndrome.
Br J Radiol, 70 (1997), pp. 215-218
[18.]
L.L. Wang, A. Gannavarapu, C.A. Kozinetz, M.L. Levy, R.A. Lewis, M.M. Chintagumpala, et al.
Association between osteosarcoma and deleterious mutations in the RECQ4 gene in Rothmund-Thompson syndrome.
J Natl Cancer Inst, 95 (2003), pp. 669-674
[19.]
A. Longhi, M.S. Benassi, L. Molendini, M. Macchiagodena, P. Picci, G. Bacci.
Osteosarcoma in blood relatives.
Oncology Rep, 8 (2001), pp. 131-136
[20.]
G.D. Letson, C.A. Muro-Cacho.
Genetic and molecular abnormalities in tumors of the bone and soft tissues.
Cancer Control, 8 (2001), pp. 239-251
[21.]
J.M. Lipton, N. Federman, Y. Khabbaze, C.L. Schwartz, L.M. Hilliard, H.I. Clark, et al.
Osteogenic sarcoma associated with Diamond- Blackfand anemia: A report from the Diamond-Blackfand Anemia Registry.
J Pediatr Hematol Oncol, 23 (2001), pp. 39-44
[22.]
L. Orme, R. Gorlick, P. Meyers, E. Athanasian, A. Huvos.
Osteosarcoma associated with absent thums: A report of two cases.
J Pediatr Hematol Oncol, 22 (2000), pp. 73-77
[23.]
M.P. Finkel, B.O. Biskis.
Experimental induction of osteogenic sarcoma.
Prog Exp Tumor Res, 10 (1968), pp. 72-77
[24.]
B. Le Vu, F. De Vathaire, A. Shamsaldin, M.M. Hawkins, E. Grimand, C. Hardiman, et al.
Radiation dose, chemotheraphy and risk of osteosarcoma after solid tumors during childhood.
Int J Cancer, 77 (1998), pp. 370-377
[25.]
U. S. Environmental Protection Agency. Supplemental Guidance for Assesing Cancer Susceptibility from Early-Life Exposure to Carcinogens. EPA/630/R-03/003F. March. 2005. Disponible en: http://www.epa.gov/ncea/raf/cancer2003.htm
[26.]
J.D. Boice Jr, C.E. Land, D.L. Preston.
Ionizing Radiation.
Cancer epidemiology and prevention, 2nd ed., pp. 319-354
[27.]
International Agency for Reasearch on Cancer. Ionizing Radiation Part I, X-Radiation and Radiation and Neutrons.
IARC Press, (2000),
[28.]
International Agency for Reasearch on Cancer Ionizing Radiation Part II: some internally deposited radionuclides.
IARC Press, (2001),
[29.]
M.M. Hawkins, L.M.K. Wilson, H.S. Burton, M.H. Potok, D.L. Winter, H.B. Marsden, et al.
Radiotherapy, alkylating agents, and risks of bone cancer after childhood cancer.
J Natl Cancer Inst, 88 (1996), pp. 270-278
[30.]
M.A. Tuckner, A.T. Meadows, J.D. Boice Jr.
Cancer risk following treatment of childhood cancer.
Radiation carcinogenesis: Epidemiology and biological significance, pp. 211-224
[31.]
United Nations Scientific Committee on the Effects of Atomic Radiation: Sources and Effects of Ionizing Radiation. New York, United Nations Publ E-94-IX-11, 1994.
[32.]
K. Yamasaki, A. Yamasaki, M. Tosaki, Y. Isozumi, H. Hiai.
Tissue distribution of Thorotrast and role of internal irradiation in carcinogenesis.
Oncol Rep, 12 (2004), pp. 733-738
[33.]
D.J. Pritchard, M.P. Finkel, C.A. Reilly.
The etiology of osteosarcoma: A review of current considerations.
Clin Orthop, 111 (1975), pp. 14-22
[34.]
M.P. Finkel, B.O. Biskis, P.B. Jinkins.
Virus induction of osteosarcomas in mice.
Science, 151 (1996), pp. 698-701
[35.]
J.S. Colt, A. Blair.
Parental occupational exposures and risk of childhood cancer.
Environ Health Perspect, 106 (1998), pp. 909-925
[36.]
M. Feychting, N. Plato, G. Nise, A. Ahlbom.
Parental occupational exposures and childhood cancer.
Environ Health Perspect, 109 (2001), pp. 193-196
[37.]
J. Little.
Epidemiology of Childhood Cancer. International Agency for Research on Cancer. IARC Scientific Publ n.° 149.
IARC Press, (1999),
[38.]
L.M. O’Leary, A.M. Hicks, J.M. Peters, S. London.
Parental exposures and risk of childhood cancer: A review.
Am J Ind Med, 20 (1991), pp. 17-35
[39.]
K.H. Gelberg, E.F. Fitzgerald, S.A. Hwang, R. Dubrow.
Growth and development and other risk factors for osteosarcoma and Ewing's sarcoma in children and young adults.
Intern J Epidemiol, 26 (1997), pp. 272-278
[40.]
J.D. Buckley, T.W. Pendergrass, C.M. Buckley, D.J. Pritchard, M.E. Nesbit, A.J. Provisor, et al.
Epidemiology of osteosarcoma in childhood.
Cancer, 83 (1998), pp. 1440-1448
[41.]
L. Hum, N. Kreiger, M.M. Finkelstein.
The relationship between parental occupation and cancer risk in offspring.
Intern J Epidemiol, 27 (1998), pp. 766-771
[42.]
E.A. Operkalsky, S. Preston-Martin, B.E. Henderson, B.R. Visscher.
A case-control study of osteosarcoma in young persons.
Am J Epidemiol, 126 (1987), pp. 118-126
[43.]
P. Kristensen, A. Andersen, L.M. Irgens, A.S. Bye, L. Sundheim.
Cancer in offspring of parents engaged in agricultural activities in Norway: Incidence and risk factors in the farm environment.
[44.]
J.A. Schwartzbaum, S.L. George, C.B. Pratt, B. Davis.
An exploratory study of environmental and medical factors potentially related to childhood cancer.
Med Pediatr Oncol, 19 (1991), pp. 115-121
[45.]
M. Paulussen, B. Fröhlich, H. Jürgens.
Ewing's tumour: Incidence, prognosis and treatment options.
Paediatr Drugs, 3 (2001), pp. 899-913
[46.]
E. Alava, W.L. Gerald.
Molecular biology of the Ewing's sarcoma/ Primitive neuroectodermal tumor family.
J Clin Oncol, 18 (2000), pp. 204-213
[47.]
J. Kim, J. Pelletier.
Molecular genetics of chromosome translocations involving EWS and related family members.
Physiol Genomics, 1 (1999), pp. 127-138
[48.]
S.A. Burchill.
Ewing's sarcoma: diagnostic, prognostic and therapeutic implications of molecular abnormaties.
J Clin Pathol, 56 (2003), pp. 96-102
[49.]
A.L. Hartley, J.M. Birch, V. Blair, M.D. Teare, H.B. Marsden, M. Harris.
Cancer incidente in the familias of children with Ewing's tumors.
J Natl Cancer Inst, 83 (1991), pp. 955-956
[50.]
B. Novakovic, A.M. Goldstein, L.H. Wexler, M.A. Tuckner.
Increased risk of neuroectodermal tumors and stomach cancer in relativies with Ewing's sarcoma family of tumors.
J Natl Cancer Inst, 86 (1994), pp. 1702-1706
[51.]
D.M. Winn, F.P. Li, L.L. Robison, J.J. Mulvihill, A.E. Daigle, J.F. Fraumeni Jr..
A case-control study of the etiology of Ewing's sarcoma.
Cancer Epidemiol Biomarkers Prev, 1 (1992), pp. 525-532
[52.]
E.A. Holly, D.A. Aston, D.K. Ahn, J.J. Kristiansen.
Ewing's bone sarcoma, paternal occupational exposure, and other factors.
Am J Epidemiol, 138 (1992), pp. 122-129
[53.]
H.O. Adami, D. Hunter, D. Trichopoulos.
Textbook of cancer epidemiology.
Oxford University Press, (2002),
[54.]
J.U. Cope, M. Tsokos, L.J. Herman, G. Gridley, M.A. Tuckner.
Inguinal hernia in patients with Swing sarcoma: A clue to etiology.
Med Pediatr Oncol, 34 (2000), pp. 195-199
[55.]
P. Casarolli-Valery, W. McWhirter, A. Sleigh, G. Williams, C. Bain.
A national case-control study of Ewing's sarcoma family of tumors in Australia.
Int J Cancer, 105 (2003), pp. 825-830
[56.]
J. Ferrís i Tortajada, J.A. Ortega García, A. Marco Macián, J. Garcia i Castell.
Medio ambiente y cáncer pediátrico.
An Pediatr (Barc), 61 (2004), pp. 42-50
[57.]
World Health Organization. Healthy Environments for Children Alliance. Disponible en: http://www.who.int/heca/en/
[58.]
A European Environment and Health Strategy. Commission to the Council, the European Parlament and the European Economic and Council Committee. Brussels, 11-6-2003. Disponible en: http://europa.eu.int/eur-lex/en/com/cnc/2003/com.2003_0338en01.pdf
[59.]
J. Ferrís i Tortajada, J.A. Ortega García, B. López Ibor.
La etiología y la prevención del cáncer pediátrico.
An Pediatr (Barc), 61 (2004), pp. 1-4

Trabajo financiado parcialmente por la Fundación Científica de la AECC (MAPACE-2004) y por el Programa de Capacitación en Salud Ambiental y Ocupacional del Mount Sinai Medical Center, con el apoyo del Fogarty International Center (NIH TW00640).

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