Amyotrophic Lateral Sclerosis Mortality in 1.9 Million US Cancer Survivors

Abstract

Background: Large cancer registries offer the opportunity to explore and generate hypotheses about the pathogenesis of cancer and other diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Methods: Using data from nine population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the US National Cancer Institute (NCI) and death certificates, we followed 1.9 million cancer survivors who were diagnosed between 1973 and 2000 and who survived at least 1 year, through the year 2000. The outcome of interest was the standardized mortality ratio (SMR) of observed to expected ALS deaths among cancer survivors. To assess the validity of the study design, we also examined associations with Parkinson’s disease mortality, which we expected to be inversely associated with smoking-related cancers. Results: There was no significantly increased risk or deficit of ALS mortality for all cancer sites combined (SMR = 1.0). Parkinson’s disease mortality was, as expected, significantly and inversely associated with smoking-related cancers. Both ALS and Parkinson’s disease mortality were significantly elevated following melanoma (SMR = 1.6; 95% CI = 1.1–2.2; SMR = 1.5; 1.2–1.8, respectively). Contrary to previous hypotheses, ALS was unrelated to lymphomas or lymphoproliferative malignancies and was not associated with smoking-related cancers. Conclusions: In this exploratory study, we observed a modest, significant association between melanoma and both ALS and Parkinson’s disease mortality. It would be useful to explore these findings in other large national databases that are able to link cancer and ALS and Parkinson’s disease.

Mortality due to Amyotrophic Lateral Sclerosis and Parkinson’s Disease among Melanoma Patients

“…This study supports the results of earlier studies [7,8] in finding an increased risk of mortality due to ALS and PD among people previously diagnosed as having melanoma. An earlier analysis of a cohort of 1 14,000 patients with a diagnosis of PD [6] also found an almost 2-fold increased risk of malignant melanoma.…”

“…There is some evidence of a common genetic susceptibility to ALS and other neurodegenerative disorders such as PD and dementia [28] , however this evidence is not consistent [29] . There is also a suggestion that causation relates to the shared embryonic lineage of neurons and melanocytes in neural crest cells [7,30] . In addition, serotonin (5-HT) has been strongly linked with motor neuron behaviour, and mammalian skin can produce 5-HT and transform it into melatonin [31] .…”

“…In particular there has been some evidence of an association between PD and melanoma [5] . A recent study [7] in the USA found an increased risk of mortality due to PD as well as ALS among a cohort of melanoma patients. A separate study looking at non-cancer causes of death among people diagnosed as having cancer in Queensland, Australia, [8] also found evidence of increased mortality risk due to ALS and PD among the melanoma cohort.…”

“…Other empirical evidence, particularly on a population-wide basis, of associations between melanoma and ALS or PD is limited [7] . We conducted a populationbased study of the risk of mortality due to PD and ALS in people diagnosed as having melanoma in the whole of Australia.…”

Meta-analysis of the relationship between Parkinson disease and melanoma

“…We did not include 2 studies 26,27 that examined PD mortality among people previously diagnosed with melanoma. Our reasoning was that mortality was determined by both incidence and survival, which in addition to the inaccuracy of using death certificates in identifying The log odds ratio (OR) from each study is plotted on the horizontal axis, and standard error (SE) on the vertical axis.…”