Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

Agalliu, Ilir; Ortega, Roberto A.; Luciano, Marta San; Mirelman, Anat; Pont‐Sunyer, Claustre; Brockmann, Kathrin; Vilas, Dolores; Tolosa, Eduardo; Berg, Daniela; Warø, Bjørg; Glickman, Amanda; Raymond, Deborah; Inzelberg, Rivka; Ruíz‐Martínez, Javier; Mondragón, Elisabet; Friedman, Eitan; Hassin‐Baer, Sharon; Alcalay, Roy N.; Mejia‐Santana, Helen; Aasly, Jan; Foroud, Tatiana; Marder, Karen; Giladi, Nir; Bressman, Susan; Saunders‐Pullman, Rachel

doi:10.1002/mds.27807

Cited by 23 publications

(25 citation statements)

References 27 publications

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“…It is highly likely that genetic factors reduce or increase the susceptibility of PD patients to malignant neoplasms. This is supported by reports of an increased risk of various cancers among patients with LRRK2 mutations [ 10 , 47 , 48 ]. It has been found that the LRRK2 G2019S mutation was associated with an increased risk of skin and breast cancer and the R1441C/G mutation, with the risk of colon cancer and hematological cancers.…”

Section: Epidemiologic Links Between Parkinson’s Disease and Cancesupporting

confidence: 61%

“…In many studies, the morbidity associated with majority of neoplasms is lower among patients with PD than in the general population. However, melanoma, brain tumors, thyroid gland cancer, and breast cancer were found to be related with higher risks in PD patients [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Additionally, an increased rate of patients affected by kidney and uterus cancers among PD patients was observed [ 19 ].…”

Section: Epidemiologic Links Between Parkinson’s Disease and Cancementioning

confidence: 99%

“…Comparing patients with IPD and patients with LRRK2-PD, the latter had a significantly increased risk of breast cancer, hormone-related cancers, and non-skin cancer [ 49 ]. In a study comparing patients with IPD, patients with LRRK2-PD, and persons from a control group, the patients with LRRK2-PD had a 4.6-fold increased risk of leukemia compared to the IPD patients and to the control group [ 10 ]. Additionally, mutations of other PARK genes found in familial forms of PD can increase the risk of developing cancer.…”

Section: Epidemiologic Links Between Parkinson’s Disease and Cancementioning

confidence: 99%

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The Links between Parkinson’s Disease and Cancer

et al. 2020

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Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson’s disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers’ growth, and its expression may be associated with some tumors’ suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

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Section: Epidemiologic Links Between Parkinson’s Disease and Cancesupporting

confidence: 61%

Section: Epidemiologic Links Between Parkinson’s Disease and Cancementioning

confidence: 99%

Section: Epidemiologic Links Between Parkinson’s Disease and Cancementioning

confidence: 99%

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The Links between Parkinson’s Disease and Cancer

et al. 2020

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“…The absence of genetic data to establish a biological basis for the aforementioned associations and the inability to replicate recently reported cancer risks from PD-associated mutations (27) are major limitations of our study. Other shortcomings are inherent to the retrospective design of this study, including the likelihood of missing relevant data.…”

Section: Discussionmentioning

confidence: 97%

Skin Cancer May Delay Onset but Not Progression of Parkinson's Disease: A Nested Case-Control Study

et al. 2020

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Objective: To evaluate the extent to which cancer, a biological opposite to neurodegenerative disorders, may affect the onset and progression of Parkinson's disease (PD). Methods: A nested case-control design in consecutive PD patients with (cases) vs. without (controls) cancer was used to compare time to clinical diagnosis and time to Hoehn & Yahr (H&Y) staging score ≥ 3 as a measure of progression. Further, we compared PD onset and progression between cases with cancer diagnosis before (cancer before PD group) and after (cancer after PD group) PD onset. Independent variables were age at PD onset, motor subscale of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, sex, cognitive impairment, falls, depression, anxiety, dementia, and autonomic symptoms. Time to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR). Group differences were evaluated using unpaired t-test or Fisher's exact test. Results: The clinical PD onset was later in cases vs. controls (median 67.2 vs. 59.8 years; p < 0.001), but the adjusted time to H&Y ≥ 3 was similar between groups (HR = 0.67; p = 0.13). Skin cancers constituted 75% of all cancers in cases. Amongst skin cancers, compared to controls, cases had an older age at PD onset (67.8 vs. 59.8 years; p < 0.001). There was no difference in risk of progression in PD patients with skin cancer compared to controls (HR = 0.54, p = 0.09). Conclusions: Cancer, in particular of the skin, may delay the onset but not the progression of PD. Future prospective observational studies are warranted to elucidate the complex interactions between these biologically divergent disorders.

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“…Alterations in this gene may play a role in cancer progression and response to chemotherapy in several types of cancer (20)(21)(22)(23)(24)(25)(26). Some genes, such as LRRK2 and PRKN, may be associated with both cancer and PD (27)(28)(29)(30). GALNT14 contributes to breast cancer invasion by altering cell proliferation and motility, by altering the expression levels of EMT genes, and by stimulating MMP-2 activity (31).…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease

et al. 2020

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Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown. Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD. Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD. Results: FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8-4.8, P = 6.5 × 10 −6 ]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9-10.3, P = 7.88 × 10 −9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction. Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings.

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Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

Cited by 23 publications

References 27 publications

The Links between Parkinson’s Disease and Cancer

The Links between Parkinson’s Disease and Cancer

Skin Cancer May Delay Onset but Not Progression of Parkinson's Disease: A Nested Case-Control Study

Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease

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