Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions

Abstract

Several epidemiological studies support low cancer rates in patients with neurodegenerative disorders, including Parkinson's disease, Huntington's disease, and Alzheimer's disease. Different mechanisms were raised as possible causes, from mutated tumor suppressor genes (PARKIN, PINK1) to small interfering RNA based on the CAG trinucleotide repeat expansions located in introns or untranslated regions. However, as every rule has an exception, some tumors have an increased incidence in these neurodegenerative diseases such as breast and skin cancer (melanoma). This mini-review aims to establish the epidemiology between these neurodegenerative disorders and cancer to determine the possible mechanisms involved and therefore set eventual therapeutic applications. According to our findings, we conclude the presence of an inverse relationship among most cancers and the aforementioned neurodegenerative disorders. However, this concept needs to be considered cautiously considering specific genetic and extra-genetic linkage factors for particular tumors.

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

“…Nevertheless, the epidemiological data suggest a pattern of lower-than-expected combined probability of cancer and neurodegenerative diseases, which has been defined as “inverse comorbidity” [ 22 ]. The study of the mechanisms behind this pattern of inverse comorbidity could influence therapeutic interventions and provide strategies that prevent or delay both cancer and neurodegenerative diseases [ 19 , 23 , 24 , 25 ].…”

“…Mutations in PRKN (PARK2, Parkin), PARK7 (DJ-1), and PINK1 genes, which are among the genes contributing to familial cases of PD, lead to the mutation of both tumor suppressor genes, PTEN and TP53 [ 25 ]. On the other hand, PRKN and PARK5 have antiproliferative properties and are often inactivated in tumors [ 37 ]; PINK1 can also have antiproliferative functions [ 38 ].…”

“…Recently, a genome-wide association study (GWAS) has highlighted genes potentially involved in AD and in five different cancers (colon, breast, prostate, ovary, lung), with some shared variants modulating disease risk in a concordant way and others exerting effects in opposite directions [ 41 ]. On the other hand, the transcription factor P53 (a tumor suppressor) has multiple functions common to cancer and neurodegenerative disorders such as HD, PD, and AD [ 25 , 42 ], and it is crucial for cell growth control and apoptosis. Its expression is upregulated in AD, PD, and HD but downregulated in the vast majority of tumors [ 19 , 23 , 25 ].…”

“…On the other hand, the transcription factor P53 (a tumor suppressor) has multiple functions common to cancer and neurodegenerative disorders such as HD, PD, and AD [ 25 , 42 ], and it is crucial for cell growth control and apoptosis. Its expression is upregulated in AD, PD, and HD but downregulated in the vast majority of tumors [ 19 , 23 , 25 ].…”

Breast cancer in schizophrenia could be interleukin-33-mediated

“…In recent years, epidemiological evidence of a controversial association between cancer and neurodegenerative diseases has been increasing. Common etiological factors may play opposing roles in the pathogenesis of neurodegeneration and breast cancer[ 14 , 15 ]. Characteristic brain pathology leads to neuronal cell death and neurodegeneration over time, whereas cancer is dominated by the process of unlimited cell proliferation[ 16 , 17 ].…”