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Background: Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties., Objective: We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors., Methods: We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses., Results: We confirmed a previously reported positive genetic correlation of PD with melanoma (G corr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G corr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31)., Conclusions: We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinson's disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin-MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD., Methods: The inclusion criteria were patients with ET and untreated "de novo" PD patients; in addition, age-matched controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla to visualize neuromelanin. The primary outcomes were the area and width of the SN region with high signal., Results: A total of 15 ET patients and 12 "de novo" PD patients were evaluated. The area and width of the T1 high signal in the SN region were markedly decreased in the PD group compared with the ET and age-matched controls, and a greater decrease was seen in the ventrolateral segment. The neuromelanin measures in the ET group, although slightly lower, were not significantly different from the healthy control group. We obtained a sensitivity of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD., Conclusions: Neuromelanin-sensitive MRI techniques can discriminate ET from early-stage tremor-dominant PD and can be a useful clinical tool in the evaluation of tremor disorders. © 2015 International Parkinson and Movement Disorder Society., (© 2015 International Parkinson and Movement Disorder Society.)

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies., (Copyright 2007 Movement Disorder Society)

Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are the most frequent known cause of Parkinson's disease (PD), but their prevalence varies markedly between populations. Here we studied the frequency and associated phenotype of four recurrent LRRK2 mutations (R1441C, R1441G, R1441H, and G2019S) in familial and sporadic PD from a single referral center in Lisbon, Portugal. Among 138 unrelated PD probands, we identified 9 heterozygous G2019S carriers (6.52%) and 1 heterozygous R1441H carrier (0.72%). The G2019S mutation was present in 4 of the 107 sporadic (3.74%) and in 5 of the 31 familial probands (16.1%). Mutations were not found among 101 Portuguese controls. The G2019S mutation was present on a single haplotype and displayed reduced penetrance. Heterozygous parkin gene mutations were also found in 2 G2019S-positive probands, but their pathogenic role is unclear. The clinical phenotype in patients with LRRK2 mutations was indistinguishable from that of typical PD, including impaired sense of smell. The G2019S mutation is a very common genetic determinant among the Portuguese patients with PD, and the R1441H mutation is also present in this population. These data have important implications for the diagnostic work-up and genetic counseling of patients with this disease in Portugal.