Cancer Causes & Control

, Volume 24, Issue 1, pp 55–60 | Cite as

The association between cancer and amyotrophic lateral sclerosis

  • D. Michal Freedman
  • Rochelle E. Curtis
  • Sarah E. Daugherty
  • James J. Goedert
  • Ralph W. Kuncl
  • Margaret A. Tucker
Original paper



Increasing evidence suggests that some neurodegenerative disorders, such as Parkinson’s disease, are inversely related to cancer. Few epidemiologic studies have examined the relationship between cancer and amyotrophic lateral sclerosis (ALS), another major neurodegenerative disease. This study addresses that gap.


Using data from 16 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute and death certificates, we followed 2.7 million cancer survivors who were diagnosed between 1973 and 2007, and who survived at least 1 year following cancer diagnosis. The standardized mortality ratio (SMR) of observed to expected ALS deaths in cancer survivors was calculated.


A total of 1,216 ALS deaths were reported among 1 year survivors of cancer over 16.6 million person-years of follow-up. ALS mortality was not significantly associated with the incidence of total cancers [SMR = 1.00 (95 % confidence interval (CI), 0.95–1.06)]. There was, however, a significantly elevated risk of ALS death among survivors of melanoma [SMR = 1.49 (95 % (CI), 1.17–1.85)] and of tongue cancer [SMR = 2.57 (95 % CI, 1.41–4.32)], and a significantly reduced ALS death risk among prostate cancer survivors [SMR = 0.86 (95 % CI, 0.76–0.96)].


Cancer at certain sites may be related to risk of ALS death. Possible biologic factors linking ALS to these cancers are discussed. Future studies should attempt to confirm these associations using incident ALS outcomes. Establishing relationships between cancer and neurodegenerative diseases, such as ALS, opens new opportunities for understanding related pathophysiologic and therapeutic possibilities for these diseases.


Amyotrophic lateral sclerosis Neoplasms Melanoma Tongue neoplasms Prostatic neoplasms 



This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the U.S. Public Health Service of the Department of Health and Human Services. We thank Jeremy Miller of Information Management Services, Inc. for biomedical computer assistance and Dr. Robert J. Biggar of Queensland University of Technology for his helpful comments.

Conflict of interest



  1. 1.
    Plun-Favreau H, Lewis PA, Hardy J, Martins LM, Wood NW (2010) Cancer and neurodegeneration: between the devil and the deep blue sea. PLoS Genet 6:e1001257PubMedCrossRefGoogle Scholar
  2. 2.
    Tabares-Seisdedos R, Dumont N, Baudot A et al (2011) No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. Lancet Oncol 12:604–608PubMedCrossRefGoogle Scholar
  3. 3.
    Devine MJ, Plun-Favreau H, Wood NW (2011) Parkinson’s disease and cancer: two wars, one front. Nat Rev Cancer 11:812–823Google Scholar
  4. 4.
    Roe CM, Fitzpatrick AL, Xiong C et al (2010) Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74:106–112PubMedCrossRefGoogle Scholar
  5. 5.
    Bajaj A, Driver JA, Schernhammer ES (2010) Parkinson’s disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control 21:697–707PubMedCrossRefGoogle Scholar
  6. 6.
    Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Moller H (2005) Atypical cancer pattern in patients with Parkinson’s disease. Br J Cancer 92:201–205PubMedCrossRefGoogle Scholar
  7. 7.
    Driver JA, Logroscino G, Buring JE, Gaziano JM, Kurth T (2007) A prospective cohort study of cancer incidence following the diagnosis of Parkinson’s disease. Cancer Epidemiol Biomarkers Prev 16:1260–1265PubMedCrossRefGoogle Scholar
  8. 8.
    Driver JA, Beiser A, Au R et al (2012) Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ 344:e1442PubMedCrossRefGoogle Scholar
  9. 9.
    Olsen JH, Friis S, Frederiksen K (2006) Malignant melanoma and other types of cancer preceding Parkinson disease. Epidemiology 17:582–587PubMedCrossRefGoogle Scholar
  10. 10.
    Freedman DM, Travis LB, Gridley G, Kuncl RW (2005) Amyotrophic lateral sclerosis mortality in 1.9 million US cancer survivors. Neuroepidemiology 25:176–180PubMedCrossRefGoogle Scholar
  11. 11.
    Baade PD, Fritschi L, Freedman DM (2007) Mortality due to amyotrophic lateral sclerosis and Parkinson’s disease among melanoma patients. Neuroepidemiology 28:16–20PubMedCrossRefGoogle Scholar
  12. 12.
    Zisfein J, Caroscio JT (1988) No association of amyotrophic lateral sclerosis with cancer. Mt Sinai J Med 55:159–161PubMedGoogle Scholar
  13. 13.
    Chio A, Brignolio F, Meineri P, Rosso MG, Tribolo A, Schiffer D (1988) Motor neuron disease and malignancies: results of a population-based study. J Neurol 235:374–375PubMedCrossRefGoogle Scholar
  14. 14.
    Kurtzke JF, Beebe GW (1980) Epidemiology of amyotrophic lateral sclerosis: 1. A case–control comparison based on ALS deaths. Neurology 30:453–462PubMedCrossRefGoogle Scholar
  15. 15.
    Kondo K (1984) Motor neuron disease and Parkinson’s disease are not associated with other disorders at autopsy. Neuroepidemiology 3:182–194CrossRefGoogle Scholar
  16. 16.
    Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700PubMedCrossRefGoogle Scholar
  17. 17.
    Kiernan MC, Vucic S, Cheah BC et al (2011) Amyotrophic lateral sclerosis. Lancet 377:942–955PubMedCrossRefGoogle Scholar
  18. 18.
    Logroscino G, Traynor BJ, Hardiman O et al (2008) Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry 79:6–11PubMedCrossRefGoogle Scholar
  19. 19.
    Steenland K, MacNeil J, Seals R, Levey A (2010) Factors affecting survival of patients with neurodegenerative disease. Neuroepidemiology 35:28–35PubMedCrossRefGoogle Scholar
  20. 20.
    Mateen FJ, Carone M, Sorenson EJ (2010) Patients who survive 5 years or more with ALS in Olmsted County, 1925–2004. J Neurol Neurosurg Psychiatry 81:1144–1146PubMedCrossRefGoogle Scholar
  21. 21.
    Chio A, Logroscino G, Hardiman O et al (2009) Prognostic factors in ALS: a critical review. Amyotroph Lateral Scler 10:310–323PubMedCrossRefGoogle Scholar
  22. 22.
    Curtis RE, Freedman DM, Ron E, Ries LAG, Hacker DG, Edwards BK, Tucker MA, Fraumeni JF Jr (2006) New malignancies among cancer survivors: SEER cancer registries, 1973–2000. National Cancer Institute, BethesdaGoogle Scholar
  23. 23.
    Swan J, Wingo P, Clive R et al (1998) Cancer surveillance in the U.S.: can we have a national system? Cancer 83:1282–1291PubMedCrossRefGoogle Scholar
  24. 24.
    Leone M, Chandra V, Schoenberg BS (1987) Motor neuron disease in the United States, 1971 and 1973–1978: patterns of mortality and associated conditions at the time of death. Neurology 37:1339–1343PubMedCrossRefGoogle Scholar
  25. 25.
    Barry MJ (2001) Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. N Engl J Med 344:1373–1377PubMedCrossRefGoogle Scholar
  26. 26.
    Baade PD, Herrero Hernandez E, Freedman DM, Smithers BM, Fritschi L (2010) No role for melanoma treatment in the association between melanoma and amyotrophic lateral sclerosis or Parkinson’s disease. Neuroepidemiology 35:303–304PubMedCrossRefGoogle Scholar
  27. 27.
    Habib AA, Mitsumoto H (2011) Emerging drugs for amyotrophic lateral sclerosis. Expert Opin Emerg Drugs 16:537–558PubMedCrossRefGoogle Scholar
  28. 28.
    Lee HJ, Wall BA, Wangari-Talbot J et al (2011) Glutamatergic pathway targeting in melanoma: single-agent and combinatorial therapies. Clin Cancer Res 17:7080–7092PubMedCrossRefGoogle Scholar
  29. 29.
    Stepulak A, Luksch H, Gebhardt C et al (2009) Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol 132:435–445PubMedCrossRefGoogle Scholar
  30. 30.
    Speyer CL, Smith JS, Banda M, Devries JA, Mekani T, Gorski DH (2012) Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer. Breast Cancer Res Treat 132:565–573Google Scholar
  31. 31.
    Yip D, Le MN, Chan JL et al (2009) A phase 0 trial of riluzole in patients with resectable stage III and IV melanoma. Clin Cancer Res 15:3896–3902PubMedCrossRefGoogle Scholar
  32. 32.
    Cavalheiro EA, Olney JW (2001) Glutamate antagonists: deadly liaisons with cancer. Proc Natl Acad Sci USA 98:5947–5948PubMedCrossRefGoogle Scholar
  33. 33.
    Yasui K, Oketa Y, Higashida K, Fukazawa H, Ono S (2011) Increased progranulin in the skin of amyotrophic lateral sclerosis: an immunohistochemical study. J Neurol Sci 309:110–114PubMedCrossRefGoogle Scholar
  34. 34.
    Watanabe T, Okeda Y, Yamano T, Ono S (2010) An immunohistochemical study of ubiquitin in the skin of sporadic amyotrophic lateral sclerosis. J Neurol Sci 298:52–56PubMedCrossRefGoogle Scholar
  35. 35.
    Suzuki M, Mikami H, Watanabe T et al (2010) Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosis. Acta Neurol Scand 122:367–372PubMedCrossRefGoogle Scholar
  36. 36.
    Nomura M, Oketa Y, Yasui K, Ishikawa H, Ono S (2012) Expression of hepatocyte growth factor in the skin of amyotrophic lateral sclerosis. Acta Neurol Scand 125:389–397Google Scholar
  37. 37.
    Bogenrieder T, Herlyn M (2010) The molecular pathology of cutaneous melanoma. Cancer Biomark 9:267–286PubMedGoogle Scholar
  38. 38.
    Park SY, Lee SA, Han IH et al (2007) Clinical significance of metabotropic glutamate receptor 5 expression in oral squamous cell carcinoma. Oncol Rep 17:81–87PubMedGoogle Scholar
  39. 39.
    Kasper JS, Liu Y, Giovannucci E (2009) Diabetes mellitus and risk of prostate cancer in the health professionals follow-up study. Int J Cancer 124:1398–1403PubMedCrossRefGoogle Scholar
  40. 40.
    Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM (2009) Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer 124:2416–2429PubMedCrossRefGoogle Scholar
  41. 41.
    Sakowski SA, Schuyler AD, Feldman EL (2009) Insulin-like growth factor-I for the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10:63–73PubMedCrossRefGoogle Scholar
  42. 42.
    Sorenson EJ, Windbank AJ, Mandrekar JN et al (2008) Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology 71:1770–1775PubMedCrossRefGoogle Scholar
  43. 43.
    Bilak MM, Kuncl RW (2001) Delayed application of IGF-I and GDNF can rescue already injured postnatal motor neurons. NeuroReport 12:2531–2535PubMedCrossRefGoogle Scholar
  44. 44.
    Marin B, Couratier P, Preux PM, Logroscino G (2011) Can mortality data be used to estimate amyotrophic lateral sclerosis incidence? Neuroepidemiology 36:29–38PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht (outside the USA)  2012

Authors and Affiliations

  • D. Michal Freedman
    • 1
  • Rochelle E. Curtis
    • 2
  • Sarah E. Daugherty
    • 3
  • James J. Goedert
    • 4
  • Ralph W. Kuncl
    • 6
  • Margaret A. Tucker
    • 5
  1. 1.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  2. 2.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  3. 3.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  4. 4.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  5. 5.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  6. 6.Department of Neurology, School of Medicine and DentistryUniversity of RochesterRochesterUSA

Personalised recommendations