Using Epidemiology and Genomics to Understand Osteosarcoma Etiology

Osteosarcoma is a primary bone malignancy that typically occurs during adolescence but also has a second incidence peak in the elderly. It occurs most commonly in the long bones, although there is variability in location between age groups. The etiology of osteosarcoma is not well understood; it occurs at increased rates in individuals with Paget disease of bone, after therapeutic radiation, and in certain cancer predisposition syndromes. It also occurs more commonly in taller individuals, but a strong environmental component to osteosarcoma risk has not been identified. Several studies suggest that osteosarcoma may be associated with single nucleotide polymorphisms in genes important in growth and tumor suppression but the studies are limited by sample size. Herein, we review the epidemiology of osteosarcoma as well as its known and suspected risk factors in an effort to gain insight into its etiology.

[1]  L. S. Schmidt,et al.  Birth characteristics and Wilms tumors in children in the Nordic countries: A register‐based case–control study , 2011, International journal of cancer.

[2]  D. Malkin Li-fraumeni syndrome. , 2001, Genes & cancer.

[3]  Pu Li,et al.  Functional polymorphisms in cell death pathway genes and risk of renal cell carcinoma , 2010, Molecular carcinogenesis.

[4]  R. Hayes,et al.  Genetic variation at chromosome 8q24 in osteosarcoma cases and controls. , 2010, Carcinogenesis.

[5]  S. Doublier,et al.  Fluoride effects: the two faces of janus. , 2010, Current medicinal chemistry.

[6]  E. Pignotti,et al.  Survival in high-grade osteosarcoma: improvement over 21 years at a single institution. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  L. Larizza,et al.  Rothmund-Thomson syndrome , 2010, Orphanet journal of rare diseases.

[8]  J. Behren,et al.  Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype , 2009, British Journal of Cancer.

[9]  Magali Olivier,et al.  TP53 mutations in human cancers: origins, consequences, and clinical use. , 2010, Cold Spring Harbor perspectives in biology.

[10]  H. Pan,et al.  TGFBR1*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls , 2010, Molecular Biology Reports.

[11]  Yong Zhang,et al.  Association between TGFBR1*6A and osteosarcoma: A Chinese case-control study , 2010, BMC Cancer.

[12]  A. Vaporciyan,et al.  Age as a prognostic factor for patients with osteosarcoma: an analysis of 438 patients , 2010, Journal of Cancer Research and Clinical Oncology.

[13]  T. Lightfoot,et al.  Birth weight, sex and childhood cancer: A report from the United Kingdom Childhood Cancer Study. , 2009, Cancer epidemiology.

[14]  R. Layfield,et al.  Recent advances in understanding the molecular basis of Paget disease of bone , 2009, Journal of Clinical Pathology.

[15]  Lisa Mirabello,et al.  International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons , 2009, International journal of cancer.

[16]  P. Picci,et al.  Effect of TP53 Arg72Pro and MDM2 SNP309 Polymorphisms on the Risk of High-Grade Osteosarcoma Development and Survival , 2009, Clinical Cancer Research.

[17]  M. Tucker,et al.  Cause-specific mortality in long-term survivors of retinoblastoma. , 2009, Journal of the National Cancer Institute.

[18]  L. Mirabello,et al.  Osteosarcoma incidence and survival rates from 1973 to 2004 , 2009, Cancer.

[19]  W. Gong,et al.  FAS promoter polymorphisms and cancer risk: a meta-analysis based on 34 case-control studies. , 2009, Carcinogenesis.

[20]  Paul D. P. Pharoah,et al.  p53 polymorphisms: cancer implications , 2009, Nature Reviews Cancer.

[21]  C. Khanna,et al.  Bridging the gap between experimental animals and humans in osteosarcoma. , 2009, Cancer treatment and research.

[22]  G. Ottaviani,et al.  The etiology of osteosarcoma. , 2009, Cancer treatment and research.

[23]  Preetha Rajaraman,et al.  Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations , 2009, Pediatric Radiology.

[24]  M. Pollak,et al.  Insulin and insulin-like growth factor signalling in neoplasia , 2008, Nature Reviews Cancer.

[25]  C. Errani,et al.  Osteosarcoma in patients older than 65 years. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  V. Bohr,et al.  The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis , 2008, Human Genetics.

[27]  R. Hayes,et al.  Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. , 2008, Human molecular genetics.

[28]  Thomas Harder,et al.  Birth weight and subsequent risk of childhood primary brain tumors: a meta-analysis. , 2008, American journal of epidemiology.

[29]  Julian Peto,et al.  Association of Genetic Variants at 8q24 with Breast Cancer Risk , 2008, Cancer Epidemiology Biomarkers & Prevention.

[30]  J. Ross,et al.  Trends in childhood cancer incidence in the U.S. (1992–2004) , 2008, Cancer.

[31]  R. Sankila,et al.  Osteosarcoma in Finland from 1971 through 1990 A nationwide study of epidemiology and outcome , 2008, Acta orthopaedica.

[32]  F. Sim,et al.  Malignant bone tumors. , 2001, Instructional course lectures.

[33]  P. Choong,et al.  A review of clinical and molecular prognostic factors in osteosarcoma , 2008, Journal of Cancer Research and Clinical Oncology.

[34]  Q. Wei,et al.  Exploratory Analysis of Fas Gene Polymorphisms in Pediatric Osteosarcoma Patients , 2007, Journal of pediatric hematology/oncology.

[35]  E. Steliarova-Foucher,et al.  Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[36]  W. Wallace,et al.  Twentieth-century survival from osteosarcoma in childhood. Trends from 1933 to 2004. , 2007, The Journal of bone and joint surgery. British volume.

[37]  M. Wallander,et al.  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 , 2007, The Prostate.

[38]  P. Scheidt,et al.  Cohort profile: the International Childhood Cancer Cohort Consortium (I4C). , 2007, International journal of epidemiology.

[39]  S. Chanock,et al.  Analysis of Genes Critical for Growth Regulation Identifies Insulin-like Growth Factor 2 Receptor Variations with Possible Functional Significance as Risk Factors for Osteosarcoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[40]  S. Chanock,et al.  Germ‐line genetic variation of TP53 in osteosarcoma , 2007, Pediatric blood & cancer.

[41]  A. Stewart,et al.  Osteosarcoma, Chondrosarcoma, and Ewing's Sarcoma: National Cancer Data Base Report , 2007, Clinical orthopaedics and related research.

[42]  M. Forman,et al.  Birthweight by gestational age and childhood cancer , 2007, Cancer Causes & Control.

[43]  A. Whittemore,et al.  Multiple regions within 8q24 independently affect risk for prostate cancer , 2007, Nature Genetics.

[44]  M. Tucker,et al.  Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. , 2007, Journal of the National Cancer Institute.

[45]  M. Gadelha,et al.  Osteosarcoma and acromegaly: A case report and review of the litereture , 2006, Journal of endocrinological investigation.

[46]  M. Hansen,et al.  Osteosarcoma in Paget's Disease of Bone , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[47]  R. Hoover,et al.  Perinatal factors, growth and development, and osteosarcoma risk , 2006, British Journal of Cancer.

[48]  K. Michels,et al.  Role of birthweight in the etiology of breast cancer , 2006, International journal of cancer.

[49]  E. Steliarova-Foucher,et al.  Cancer incidence and survival in European adolescents (1978-1997). Report from the Automated Childhood Cancer Information System project. , 2006, European journal of cancer.

[50]  E. Steliarova-Foucher,et al.  Bone tumours in European children and adolescents, 1978-1997. Report from the Automated Childhood Cancer Information System project. , 2006, European journal of cancer.

[51]  C. Douglass,et al.  Caution Needed in Fluoride and Osteosarcoma Study , 2006, Cancer Causes & Control.

[52]  D. Altshuler,et al.  Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. , 2006, Journal of the National Cancer Institute.

[53]  A. Craft,et al.  Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994 , 2005, British Journal of Cancer.

[54]  David Wypij,et al.  Age-specific Fluoride Exposure in Drinking Water and Osteosarcoma (United States) , 2006, Cancer Causes & Control.

[55]  C. Bonaïti‐pellié,et al.  Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome , 2005, Journal of Medical Genetics.

[56]  Pinchas Cohen,et al.  The role of the insulin-like growth factor system in prenatal growth. , 2005, Molecular genetics and metabolism.

[57]  K. McCaul,et al.  Primary malignant bone tumours in Western Australia, 1972–1996 , 2005, Pathology.

[58]  F. Berrino,et al.  Childhood cancer survival trends in Europe: a EUROCARE Working Group study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[59]  S. Bull,et al.  TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  E. Steliarova-Foucher,et al.  Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study , 2004, The Lancet.

[61]  A. Levine,et al.  A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans , 2004, Cell.

[62]  A. Ogose,et al.  Osteosarcomas after the Age of 50: A Clinicopathologic Study of 64 Cases—an Experience in Northern Japan , 2004, Annals of Surgical Oncology.

[63]  G. Bacci,et al.  Height as a risk factor in osteosarcoma. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  M. Pearce,et al.  Stature of young people with malignant bone tumors , 2004, Pediatric blood & cancer.

[65]  L. Robison,et al.  Big babies and infant leukemia: a role for insulin-like growth factor-1? , 1996, Cancer Causes & Control.

[66]  J. German,et al.  Bloom's syndrome , 1972, Humangenetik.

[67]  M. Melbye,et al.  Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. , 2003, American journal of epidemiology.

[68]  A. Patiño-García,et al.  Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen I&agr;1 Genes and Their Relationship With Height in Children With Bone Cancer , 2003, Journal of pediatric hematology/oncology.

[69]  Jennifer R. Harris,et al.  Heritability of adult body height: a comparative study of twin cohorts in eight countries. , 2003, Twin research : the official journal of the International Society for Twin Studies.

[70]  A. Sandberg,et al.  Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. , 2003, Cancer genetics and cytogenetics.

[71]  J. Squire,et al.  Chromosomal instability in osteosarcoma and its association with centrosome abnormalities. , 2003, Cancer genetics and cytogenetics.

[72]  E. Ron,et al.  CANCER RISKS FROM MEDICAL RADIATION , 2003, Health physics.

[73]  J. W. van der Eijken,et al.  Osteosarcoma over the age of forty. , 2003, European journal of cancer.

[74]  M. Coleman,et al.  Childhood cancer survival in Europe and the United States , 2002, Cancer.

[75]  M. Stovall,et al.  Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  Kenneth Chu,et al.  Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC , 2002, Science.

[77]  Jacques P. Brown,et al.  Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. , 2002, American journal of human genetics.

[78]  B. Carsi,et al.  Primary Osteosarcoma in Adults Older Than 40 Years , 2002, Clinical orthopaedics and related research.

[79]  W. Winkelmann,et al.  Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  J. Oshima,et al.  Werner Syndrome , 2020, Constitutional Oncogenetics.

[81]  D. Lev,et al.  Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. , 2001, American journal of medical genetics.

[82]  L. D. Da Costa,et al.  Diamond-Blackfan Anemia , 2019, Clinical Disorders and Experimental Models of Erythropoietic Failure.

[83]  J. Lipton,et al.  Osteogenic Sarcoma Associated With Diamond–Blackfan Anemia: A Report From the Diamond–Blackfan Anemia Registry , 2001, Journal of pediatric hematology/oncology.

[84]  Robert W. Miller,et al.  Atypical Osteosarcomas in Werner Syndrome (Adult Progeria) , 2000, Japanese journal of cancer research : Gann.

[85]  A. Patiño-García,et al.  Analysis of the human tumour necrosis factor-alpha (TNFα) gene promoter polymorphisms in children with bone cancer , 2000, Journal of medical genetics.

[86]  N. Jaffe,et al.  Osteosarcoma in Preadolescent Patients , 2000, Clinical orthopaedics and related research.

[87]  N. Mohandas,et al.  Diamond-Blackfan anemia , 2000, Current opinion in hematology.

[88]  J. Buckley,et al.  Epidemiology of osteosarcoma and Ewing's sarcoma in childhood , 1998, Cancer.

[89]  R. Grimer,et al.  Longitudinal Growth Following Treatment for Osteosarcoma , 1998, Sarcoma.

[90]  S. Hwang,et al.  Growth and development and other risk factors for osteosarcoma in children and young adults. , 1997, International journal of epidemiology.

[91]  E. Kramárová,et al.  The international classification of childhood cancer , 1996, International journal of cancer.

[92]  D. Lucas Dahlin’s Bone Tumors: General Aspects and Data on 11,087 Cases , 1996 .

[93]  D. Parkin,et al.  Geographic and ethnic variations in the incidence of childhood cancer. , 1996, British medical bulletin.

[94]  Y. Ishikawa,et al.  Excess of rare cancers in Werner syndrome (adult progeria). , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[95]  K. Unni,et al.  Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases , 1996 .

[96]  H. Tideman Abstract from international literatureBone cancers: H. D. Dorfman, B. Czerniak Cancer 1995: 75: 203–10 , 1995 .

[97]  L. Robison,et al.  Incidence of cancer in children in the United States. Sex‐, race‐, and 1‐year age‐specific rates by histologic type , 1995, Cancer.

[98]  H. Tsukuma,et al.  Survival Rates of Childhood Cancer Patients in Osaka, Japan, 1975–1984 , 1995, Japanese journal of cancer research : Gann.

[99]  B. Czerniak,et al.  Bone cancers , 1995, Cancer.

[100]  D. Leroith,et al.  Insulin-like Growth Factors and Cancer , 1995, Annals of Internal Medicine.

[101]  N. Breslow,et al.  Increased birth weights of National Wilms' Tumor Study patients suggest a growth factor excess. , 1994, Cancer research.

[102]  S. Hirschfeld,et al.  Human osteosarcoma cell lines are dependent on insulin-like growth factor I for in vitro growth. , 1994, Cancer research.

[103]  B. Novakovič U.S. childhood cancer survival, 1973-1987. , 1994, Medical and pediatric oncology.

[104]  D. Parkin,et al.  International variations in the incidence of childhood bone tumours , 1993, International journal of cancer.

[105]  F. Sim,et al.  Postradiation sarcoma of bone. , 1972, Orthopedics.

[106]  J. Healey,et al.  The effect of chemotherapy on growth in the skeletally immature individual. , 1991, Clinical orthopaedics and related research.

[107]  L. Strong,et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. , 1990, Science.

[108]  C. Polychronakos,et al.  Insulinlike growth factor I: a potent mitogen for human osteogenic sarcoma. , 1990, Journal of the National Cancer Institute.

[109]  J. Mann,et al.  The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): case control study of children with bone and soft tissue sarcomas. , 1988, British Journal of Cancer.

[110]  D. Parkin,et al.  The international incidence of childhood cancer , 1988, IARC scientific publications.

[111]  S. Preston‐Martin,et al.  A case-control study of osteosarcoma in young persons. , 1987, American journal of epidemiology.

[112]  C. Pui,et al.  Height at diagnosis of malignancies. , 1987, Archives of disease in childhood.

[113]  A. Huvos Osteogenic sarcoma of bones and soft tissues in older persons. A clinicopathologic analysis of 117 patients older than 60 years , 1986, Cancer.

[114]  A. Polednak Primary bone cancer incidence in black and white residents of New York state , 1985, Cancer.

[115]  N. Samaan,et al.  Hormonal evaluation in patients with osteosarcoma , 1985, Journal of surgical oncology.

[116]  W. Taylor,et al.  Trends and variability in survival among patients with osteosarcoma: a 7-year update. , 1985, Mayo Clinic proceedings.

[117]  D. Dahlin Prognostic factors in osteosarcoma. , 1980, International journal of radiation oncology, biology, physics.

[118]  L. Broström,et al.  Longitudinal growth and dental development in osteosarcoma patients. , 1980, Acta orthopaedica Scandinavica.

[119]  A. Drash,et al.  Metabolic and endocrine alterations in osteosarcoma patients , 1978, Cancer.

[120]  P. Scranton,et al.  Prognostic factors in osteosarcoma: A review of 20 years' experience at the university of pittsburgh health center hospitals , 1975 .

[121]  P. Scranton,et al.  Prognostic factors in osteosarcoma: A review of 20 years' experience at the university of pittsburgh health center hospitals , 1975, Cancer.

[122]  R. Lorentzon,et al.  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. , 1974, The Journal of bone and joint surgery. British volume.

[123]  J. Fraumeni,et al.  Epidemiology of bone cancer in children. , 1970, Journal of the National Cancer Institute.

[124]  J. Fraumeni,et al.  Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? , 1969, Annals of internal medicine.

[125]  J. Fraumeni Stature and malignant tumors of bone in childhood and adolescence , 1967, Cancer.

[126]  M. Lomicek,et al.  [Malignant bone tumors]. , 1957, Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca.

[127]  C. H. Price Osteogenic Sarconma; An Analysis of the Age and Sex Incidence , 1955, British Journal of Cancer.

[128]  G. David Roodman,et al.  Paget disease of bone , 2012, Radiopaedia.org.