Abstract
Purpose: The present study aimed at quantifying risks for second malignancies in patients with bone cancers, and risks for second bone cancers after other primary tumors. Methods: Adjusted standardized incidence ratios (SIRs) were used as a measure of risk. Results: Among 2,546 primary bone cancer patients, a total of 171-second malignancies occurred. Besides second bone cancers, other cancer sites with an increased SIR were the soft tissues and endocrine glands. The overall risk of second malignancies following Ewing’s sarcoma was 5.63, followed by chordoma (1.99), osteosarcoma (1.54), and chondrosarcoma (1.51). Patients diagnosed before age 20 years showed an increased SIR of 3.11. The increased occurrence of second bone cancers was noted after the cancer sites of upper aerodigestive tract, kidney and nervous system. Conclusions: The incidence of second primary malignancies in bone cancer patients was moderately increased. Among histological types, Ewing’s sarcoma showed the highest risk of developing second cancers. Young age was also associated with an increased risk. Besides therapeutic effects, the observed excesses of a second bone or soft tissue tumor may be related to Li-Fraumeni syndrome. Increases at other sites may be related to unknown factors or spurious findings.
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References
Aparicio J, Segura A, Montalar J, Verdeguer A, Castel V, Sanchez-Heras AB (1998) Secondary cancers after Ewing sarcoma and Ewing sarcoma as second malignant neoplasm. Med Pediatr Oncol 30:259–260
Arndt CA, Crist WM (1999) Common musculoskeletal tumors of childhood and adolescence. N Engl J Med 341:342–352
Aung L, Gorlick RG, Shi W, Thaler H, Shorter NA, Healey JH, Huvos AG, Meyers PA (2002) Second malignant neoplasms in long-term survivors of osteosarcoma: memorial sloan-kettering cancer center experience. Cancer 95:1728–1734
Bhatia S, Sklar C (2002) Second cancers in survivors of childhood cancer. Nat Rev Cancer 2:124–132
Boice JD Jr, Storm HH, Curtis RE, Jensen OM, Kleinerman RA, Jensen HS, Flannery JT, Fraumeni JF Jr (1985) Introduction to the study of multiple primary cancers. Natl Cancer Inst Monogr 68:3–9
Carnevale A, Lieberman E, Cardenas R (1997) Li-Fraumeni syndrome in pediatric patients with soft tissue sarcoma or osteosarcoma. Arch Med Res 28:383–386
Center for Epidemiology (2002) Cancer incidence in Sweden 2000. The National Board of Health and Welfare, Stockholm
Coleman MP, Gatta G, Verdecchia A, Esteve J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M, Berrino F (2003) EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Ann Oncol 14(Suppl. 5):v128–v149
Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (1992) Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors. Nature 359:162–165
Dong C, Hemminki K (2001) Second primary neoplasms in 633,964 cancer patients in Sweden, 1958–1996. Int J Cancer 93:155–161
Esteve J, Benhamou E, Raymond L (1994) Statistical methods in cancer research. IARC, Lyon
Fuchs B, Valenzuela RG, Petersen IA, Arndt CA, Sim FH (2003) Ewing’s sarcoma and the development of secondary malignancies. Clin Orthop Relat Res 415:82–89
Garwicz S, Anderson H, Olsen JH, Dollner H, Hertz H, Jonmundsson G, Langmark F, Lanning M, Moller T, Sankila R, Tulinius H (2000) Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the five Nordic countries. The Nordic society for pediatric hematology and oncology. The association of the Nordic cancer registries. Int J Cancer 88:672–678
Hawkins MM, Wilson LM, Burton HS, Potok MH, Winter DL, Marsden HB, Stovall MA (1996) Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst 88:270–278
Hemminki K, Granstrom C (2002) Risk for familial breast cancer increases with age. Nat Genet 32:233
Hemminki K, Li X, Plna K, Granstrom C, Vaittinen P (2001) The nation-wide Swedish family-cancer database–updated structure and familial rates. Acta Oncol 40:772–777
Hemminki K, Granstrom C, Chen B (2005a) The Swedish family-cancer database: update, application to colorectal cancer, and clinical relevance. Hereditary Cancer Clin Pract 3:7–18
Hemminki K, Scelo G, Boffetta P, Mellemkjaer L, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride M, Kliewer EV, Chia KS, Pompe-Kirn V, Martos C, Jonasson JG, Li X, Brennan P (2005b) Second primary malignancies in patients with male breast cancer. Br J Cancer 92:1288–1292
Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90:606–611
Kuttesch JF Jr, Wexler LH, Marcus RB, Fairclough D, Weaver-McClure L, White M, Mao L, Delaney TF, Pratt CB, Horowitz ME, Kun LE (1996) Second malignancies after Ewing’s sarcoma: radiation dose-dependency of secondary sarcomas. J Clin Oncol 14:2818–2825
Li X, Hemminki K (2002) Parental cancer as a risk factor for bone cancer: a nation-wide study from Sweden. J Clin Epidemiol 55:111–114
Lindor NM, Greene MH (1998) The concise handbook of family cancer syndromes. Mayo familial cancer program. J Natl Cancer Inst 90:1039–1071
Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238
Marec-Berard P, Philip T (2004) Ewing sarcoma: the pediatrician’s point of view. Pediatr Blood Cancer 42:477–480
McIntyre JF, Smith-Sorensen B, Friend SH, Kassell J, Borresen AL, Yan YX, Russo C, Sato J, Barbier N, Miser J (1994) Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. J Clin Oncol 12:925–930
Neugut AI, Meadows AT, Robson D (1999) Multiple primary cancers. Lippincott Williams,Wilkins, Philadelphia
Parkin DM, Stiller CA, Nectoux J (1993) International variations in the incidence of childhood bone tumors. Int J Cancer 53:371–376
Pratt CB, Meyer WH, Luo X, Cain AM, Kaste SC, Pappo AS, Rao BN, Fleming ID, Jenkins JJ (1997) Second malignant neoplasms occuring in survivors of osteosarcoma. Cancer 80:960–965
Swerdlow AJ, Barber JA, Hudson GV, Cunningham D, Gupta RK, Hancock BW, Horwich A, Lister TA, Linch DC (2000) Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18:498–509
Weber KL (2005) What’s new in musculoskeletal oncology. J Bone Joint Surg Am 87:1400–1410
Acknowledgments
Supported by Deutsche Krebshilfe, the Swedish Cancer Society and the EU, LSHC-CT-2004-503465. The family cancer database was created by linking registers maintained at Statistics Sweden and the Swedish Cancer Registry.
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Ji, J., Hemminki, K. Incidence of multiple primary malignancies among patients with bone cancers in Sweden. J Cancer Res Clin Oncol 132, 529–535 (2006). https://doi.org/10.1007/s00432-006-0100-1
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DOI: https://doi.org/10.1007/s00432-006-0100-1