Does Parkinsons Disease Dementia Reduce Cancer Risk more than Alzheimers Disease Alone?

Chen, Yu-Jung; Lin, Gen-Min; Wu, Yi; Tseng, Wei Shih; Kuo, De Jhen; Chu, Cheng I; Li, Yi Hwei

doi:10.4172/neuropsychiatry.1000222

Cited by 1 publication

(2 citation statements)

References 38 publications

(55 reference statements)

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“…Interestingly, a number of pairs of NDG disorders and site-specific cancers that showed significant inverse transcriptomic associations in our analyses have presented inverse comorbidity patterns at a population level in epidemiological research. For example, a reduced risk of lung cancer has been observed in patients with AD or PD [2,10,[18][19][20][21][22][23][24]33,34], and reduced risks of prostate and liver cancers have been detected in PD and AD patients, respectively [2,18,20,21,23,24,33,35]. In addition, the significant direct transcriptomic association found between PD and brain cancers is consistent with several observational studies that reported an increased risk of brain cancer in PD patients [22,41,42].…”

Section: Discussionsupporting

confidence: 85%

“…We observed that this apparent anti-cancer protective effect, which we term 'inverse cancer comorbidity' (ICC), is produced in many serious CNS and immune disorders [30][31][32]. In addition, a number of associations between AD and PD and site-specific cancers have been reported, including a reduction in the risk of lung cancer [2,10,[18][19][20][21][22][23][24]33,34], as well as a decrease in the risks of bladder, colorectal, and prostate cancers [2,11,[18][19][20][21][22][23]32,[34][35][36][37] and smoking-related cancers in general [38] in individuals with PD. Reduced risks of pancreatic, stomach, liver, blood, and endometrial cancers have also been observed [36,39,40].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic and Genetic Associations between Alzheimer’s Disease, Parkinson’s Disease, and Cancer

Forés-Martos

Boullosa²,

Rodrigo-Domínguez

et al. 2021

Cancers

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Alzheimer’s (AD) and Parkinson’s diseases (PD) are the two most prevalent neurodegenerative disorders in human populations. Epidemiological studies have shown that patients suffering from either condition present a reduced overall risk of cancer than controls (i.e., inverse comorbidity), suggesting that neurodegeneration provides a protective effect against cancer. Reduced risks of several site-specific tumors, including colorectal, lung, and prostate cancers, have also been observed in AD and PD. By contrast, an increased risk of melanoma has been described in PD patients (i.e., direct comorbidity). Therefore, a fundamental question to address is whether these associations are due to shared genetic and molecular factors or are explained by other phenomena, such as flaws in epidemiological studies, exposure to shared risk factors, or the effect of medications. To this end, we first evaluated the transcriptomes of AD and PD post-mortem brain tissues derived from the hippocampus and the substantia nigra and analyzed their similarities to those of a large panel of 22 site-specific cancers, which were obtained through differential gene expression meta-analyses of array-based studies available in public repositories. Genes and pathways that were deregulated in both disorders in each analyzed pair were examined. Second, we assessed potential genetic links between AD, PD, and the selected cancers by establishing interactome-based overlaps of genes previously linked to each disorder. Then, their genetic correlations were computed using cross-trait LD score regression and GWAS summary statistics data. Finally, the potential role of medications in the reported comorbidities was assessed by comparing disease-specific differential gene expression profiles to an extensive collection of differential gene expression signatures generated by exposing cell lines to drugs indicated for AD, PD, and cancer treatment (LINCS L1000). We identified significant inverse associations of transcriptomic deregulation between AD hippocampal tissues and breast, lung, liver, and prostate cancers, and between PD substantia nigra tissues and breast, lung, and prostate cancers. Moreover, significant direct (same direction) associations of deregulation were observed between AD and PD and brain and thyroid cancers, as well as between PD and kidney cancer. Several biological processes, including the immune system, oxidative phosphorylation, PI3K/AKT/mTOR signaling, and the cell cycle, were found to be deregulated in both cancer and neurodegenerative disorders. Significant genetic correlations were found between PD and melanoma and prostate cancers. Several drugs indicated for the treatment of neurodegenerative disorders and cancer, such as galantamine, selegiline, exemestane, and estradiol, were identified as potential modulators of the comorbidities observed between neurodegeneration and cancer.

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