The Links between Parkinson’s Disease and Cancer

Ejma, Maria; Madetko, Natalia; Brzecka, Anna; Gurański, Konstanty; Alster, Piotr; Misiuk-Hojło, Marta; Somasundaram, Siva G; Aliev, Gjumrakch

doi:10.3390/biomedicines8100416

Cited by 48 publications

(36 citation statements)

References 233 publications

(279 reference statements)

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“…4 Growing evidence suggests that PD and cancer may be associated. 5 Similar to PD, cancer incidence increases with age. 6 Smoking also modifies the risk of certain cancer, especially lung cancer, though in the opposite direction to the risk of PD.…”

Section: Introductionmentioning

confidence: 99%

Parkinson’s disease and cancer: a systematic review and meta-analysis of over 17 million participants

Zhang

Guarin

Mohammadzadehhonarvar

et al. 2021

BMJ Open

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ObjectiveTo systematically review and qualitatively evaluate epidemiological evidence on associations between Parkinson’s disease (PD) and cancer via meta-analysis.Data sourcesMEDLINE via PubMed, Web of Science and EMBASE, until March 2021.Study selectionIncluded were publications that (1) were original epidemiological studies on PD and cancer; (2) reported risk estimates; (3) were in English. Exclusion criteria included: (1) review/comments; (2) biological studies; (3) case report/autopsy studies; (4) irrelevant exposure/outcome; (5) treated cases; (6) no measure of risk estimates; (7) no confidence intervals/exact p values and (8) duplicates.Data extraction and synthesisPRISMA and MOOSE guidelines were followed in data extraction. Two-step screening was performed by two authors blinded to each other. A random-effects model was used to calculate pooled relative risk (RR).Main outcomes and measuresWe included publications that assessed the risk of PD in individuals with vs without cancer and the risk of cancer in individuals with vs without PD.ResultsA total of 63 studies and 17 994 584 participants were included. Meta-analysis generated a pooled RR of 0.82 (n=33; 95% CI 0.76 to 0.88; p<0.001) for association between PD and total cancer, 0.76 (n=21; 95% CI 0.67 to 0.85; p<0.001) for PD and smoking-related cancer and 0.92 (n=19; 95% CI 0.84 to 0.99; p=0.03) for non-smoking-related cancer. PD was associated with an increased risk of melanoma (n=29; pooled RR=1.75; 95% CI 1.43 to 2.14; p<0.001) but not for other skin cancers (n=17; pooled RR=0.90; 95% CI 0.60 to 1.34; p=0.60).ConclusionsPD and total cancer were inversely associated. This inverse association persisted for both smoking-related and non-smoking-related cancers. PD was positively associated with melanoma. These results provide evidence for further investigations for possible mechanistic associations between PD and cancer.Prospero registration numberCRD42020162103.

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Section: Introductionmentioning

confidence: 99%

Parkinson’s disease and cancer: a systematic review and meta-analysis of over 17 million participants

Zhang

Guarin

Mohammadzadehhonarvar

et al. 2021

BMJ Open

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“…Above-mentioned research point a potential role of mitochondrial impairment in PD's pathogenesis. Interestingly, comparable abnormalities are often described in carcinogenesis [39,40]. Interestingly, epidemiologic studies show a decreased incidence of most cancer types in PD except melanoma, brain tumors, thyroid and breast cancers [40].…”

Section: Parkinson's Diseasementioning

confidence: 57%

Regulation of Mitochondrial Dynamics in Parkinson’s Disease—Is 2-Methoxyestradiol a Missing Piece?

et al. 2021

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Mitochondria, as “power house of the cell”, are crucial players in cell pathophysiology. Beyond adenosine triphosphate (ATP) production, they take part in a generation of reactive oxygen species (ROS), regulation of cell signaling and cell death. Dysregulation of mitochondrial dynamics may lead to cancers and neurodegeneration; however, the fusion/fission cycle allows mitochondria to adapt to metabolic needs of the cell. There are multiple data suggesting that disturbed mitochondrial homeostasis can lead to Parkinson’s disease (PD) development. 2-methoxyestradiol (2-ME), metabolite of 17β-estradiol (E2) and potential anticancer agent, was demonstrated to inhibit cell growth of hippocampal HT22 cells by means of nitric oxide synthase (NOS) production and oxidative stress at both pharmacologically and also physiologically relevant concentrations. Moreover, 2-ME was suggested to inhibit mitochondrial biogenesis and to be a dynamic regulator. This review is a comprehensive discussion, from both scientific and clinical point of view, about the influence of 2-ME on mitochondria and its plausible role as a modulator of neuron survival.

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“…CycE has also been reported to be targeted for degradation by ubiquitination by Parkin 42 , the E3 ubiquitin ligase required for mitophagy and GSC quiescence (Fig. 3E), and this ubiquitination is Pink1-dependent 43 . Furthermore, Parkin mutations are associated with increased CycE in both cancer and Parkinson's neurons 44 .…”

Section: Cyclin E Localized To the Mitochondria Is Degraded Upon Genotoxic Or Chemical Insult In Gscs And Hipscsmentioning

confidence: 96%

Stem cell quiescence requires PRC2/PRC1-mediated mitochondrial checkpoint

Ishibashi

et al. 2021

Preprint

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Both normal and tumorous stem cells can arrest cell division, avoid apoptosis, and then regenerate lost daughter cells following acute genotoxic insult. This protective, reversible proliferative arrest, known as 'quiescence,' is still poorly understood. Here, we show that mTOR-regulated mitophagy is required for radiation insult-induced quiescence in Drosophila germline stem cells (GSCs). In GSCs, depletion of mito-fission (Drp1) or mitophagy (Pink1 and Parkin) eliminates entry into quiescence, while depletion of mitochondrial biogenesis (PGC-1alpha;) or fusion (Mfn2) eliminates exit from quiescence. We also find that mitophagy-dependent quiescence is under epigenetic control; knockdown of Jarid2 (PRC2) or Pc or Sce (PRC1) stabilizes the mitochondria and locks GSCs out of quiescence, while knockdown of PRC2-specific demethylase, Utx, prevents re-accumulation of the mitochondria and locks GSCs in quiescence. These data suggest that mitochondrial number coordinates reversible quiescence. We further identify that the mechanism of quiescence in both GSCs and human induced pluripotent stem cells (iPSCs) relies on mitophagy to deplete the mitochondrial pool of CycE and limit cell cycle progression. This alternative method of G1/S regulation may present new opportunities for therapeutic purposes.

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The Links between Parkinson’s Disease and Cancer

Cited by 48 publications

References 233 publications

Parkinson’s disease and cancer: a systematic review and meta-analysis of over 17 million participants

Parkinson’s disease and cancer: a systematic review and meta-analysis of over 17 million participants

Regulation of Mitochondrial Dynamics in Parkinson’s Disease—Is 2-Methoxyestradiol a Missing Piece?

Stem cell quiescence requires PRC2/PRC1-mediated mitochondrial checkpoint

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