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  • Original Article
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Multiple Myeloma, Gammopathies

Search for familial clustering of multiple myeloma with any cancer

Abstract

Multiple myeloma (MM) is a disease of immunoglobulin-producing plasma cells, which reside mainly in the bone marrow. Family members of MM patients are at a risk of MM, but whether other malignancies are in excess in family members is not established and is the aim of this study. MM patients (24 137) were identified from the Swedish Cancer Registry from years 1958 to 2012. Relative risks (RRs) were calculated for MM defined by any cancer diagnosed in first-degree relatives and compared with individuals whose relatives had no cancer. MM was reliably associated with relative’s colorectal, breast and prostate cancers, non-thyroid endocrine tumors, leukemia and cancer of unknown primary; in addition, MM was associated with subsites of bone and connective tissue tumors and of non-Hodgkin lymphoma, including lymphoplasmacytic lymphoma/Waldenström macroglobulinema (RR 3.47). MM showed a strong association (RR 1.91) in colorectal cancer families, possibly as part of an unidentified syndrome. All the associations of MM with discordant cancers are novel suggesting that MM shares genetic susceptibility with many cancers. The associations of MM bone and connective tissue tumors were supported by at least two independent results. Whether the results signal bone-related biology shared by MM and these tumors deserves further study.

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References

  1. Palumbo A, Anderson K . Multiple myeloma. N Engl J Med 2011; 364: 1046–1060.

    Article  CAS  PubMed  Google Scholar 

  2. Anderson KC, Carrasco RD . Pathogenesis of myeloma. Annu Rev Pathol 2011; 6: 249–274.

    Article  CAS  PubMed  Google Scholar 

  3. Morgan GJ, Johnson DC, Weinhold N, Goldschmidt H, Landgren O, Lynch HT et al. Inherited genetic susceptibility to multiple myeloma. Leukemia 2014; 28: 518–524.

    Article  CAS  PubMed  Google Scholar 

  4. Morgan GJ, Walker BA, Davies FE . The genetic architecture of multiple myeloma. Nat Rev Cancer 2012; 12: 335–348.

    Article  CAS  PubMed  Google Scholar 

  5. Landgren O . Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies. Hematology Am Soc Hematol Educ Program 2013; 2013: 478–487.

    Article  PubMed  Google Scholar 

  6. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15: e538–e548.

    Article  PubMed  Google Scholar 

  7. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M . Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol 2007; 25: 1993–1999.

    Article  PubMed  Google Scholar 

  8. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 2014; 28: 1122–1128.

    Article  CAS  PubMed  Google Scholar 

  9. Moreau P, Attal M, Facon T . Frontline therapy of multiple myeloma. Blood 2015; 125: 3076–3084.

    Article  CAS  PubMed  Google Scholar 

  10. Altieri A, Chen B, Bermejo JL, Castro F, Hemminki K . Familial risks and temporal incidence trends of multiple myeloma. Eur J Cancer 2006; 42: 1661–1670.

    Article  PubMed  Google Scholar 

  11. Landgren O, Linet MS, McMaster ML, Gridley G, Hemminki K, Goldin LR . Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: A population-based case-control study. Int J Cancer 2006; 118: 3095–3098.

    Article  CAS  PubMed  Google Scholar 

  12. Hemminki K, Li X, Czene K . Familial risk of cancer: data for clinical counseling and cancer genetics. Int J Cancer 2004; 108: 109–114.

    Article  CAS  PubMed  Google Scholar 

  13. Frank C, Fallah M, Sundquist J, Hemminki A, Hemminki K . Population landscape of familial cancer. Scientific reports 2015; 5: 12891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kristinsson SY, Bjorkholm M, Goldin LR, Blimark C, Mellqvist UH, Wahlin A et al. Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden. Int J Cancer 2009; 125: 2147–2150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hemminki K, Ji J, Brandt A, Mousavi SM, Sundquist J . The Swedish Family-Cancer Database 2009: Prospects for histology-specific and immigrant studies. Int J Cancer 2010; 126: 2259–2267.

    CAS  PubMed  Google Scholar 

  16. Breslow NE, Day NE . Statistical methods in cancer research. Volume II—The design and analysis of cohort studies. IARC Sci Publ 1987, pp 1–406.

  17. Esteve J, Benhamou E, Raymond L . Statistical Methods in Cancer Research vol. 128. IARC: Lyon, 1994.

    Google Scholar 

  18. Chen T, Fallah M, Jansen L, Castro FA, Krilavicuite A, Katalinic A et al. Distribution and risk of the second discordant primary cancers combined after a specific first primary cancer in German and Swedish cancer registries. Cancer Lett 2015; 369: 152–166.

    Article  CAS  PubMed  Google Scholar 

  19. Pavlidis N, Pentheroudakis G . Cancer of unknown primary site. Lancet 2012; 379: 1428–1435.

    Article  PubMed  Google Scholar 

  20. Hemminki K, Ji J, Sundquist J, Shu X . Familial risks in cancer of unknown primary: tracking the primary sites. J Clin Oncol 2011; 29: 435–440.

    Article  PubMed  Google Scholar 

  21. Fletcher C, Unni K, Mertens F (eds) Pathology and Genetics of Tumors of Soft Tissue and Bone. IARC Press: Lyon, 2002; p 427.

    Google Scholar 

  22. Kyle RA, Rajkumar SV . Epidemiology of the plasma-cell disorders. Best Pract Res Clin Haematol 2007; 20: 637–664.

    Article  CAS  PubMed  Google Scholar 

  23. Weires M, Bermejo JL, Sundquist J, Hemminki K . Clustering of concordant and discordant cancer types in Swedish couples is rare. Eur J Cancer 2011; 47: 98–106.

    Article  PubMed  Google Scholar 

  24. Broderick P, Chubb D, Johnson DC, Weinhold N, Forsti A, Lloyd A et al. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat Genet 2012; 44: 58–61.

    Article  CAS  Google Scholar 

  25. Chubb D, Weinhold N, Broderick P, Chen B, Johnson DC, Forsti A et al. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk. Nat Genet 2013; 45: 1221–1225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Swaminathan B, Thorleifsson G, Joud M, Ali M, Johnsson E, Ajore R et al. Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma. Nat Commun 2015; 6: 7213.

    Article  PubMed  Google Scholar 

  27. Hemminki K, Sundquist J, Brandt A . Do discordant cancers share familial susceptibility? Eur J Cancer 2012; 48: 1200–1207.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by The Multiple Myeloma Research Foundation, Deutsche Krebshilfe and The German Ministry of Education and Science (Cliommics 01ZX1309B).

Author contributions

Design: KH. Acquisition of data: JS. Statistical analysis and interpretation: CF, TC, MF, KH and AF. Manuscript writing: KH and EKM. Approval of the final text: All authors.

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Correspondence to K Hemminki.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Frank, C., Fallah, M., Chen, T. et al. Search for familial clustering of multiple myeloma with any cancer. Leukemia 30, 627–632 (2016). https://doi.org/10.1038/leu.2015.279

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