Ilir Agalliu1, Roberto A Ortega2, Marta San Luciano3, Anat Mirelman4, Claustre Pont-Sunyer5,6, Kathrin Brockmann7, Dolores Vilas5,8, Eduardo Tolosa5, Daniela Berg7,9, Bjørg Warø10, Amanda Glickman2, Deborah Raymond2, Rivka Inzelberg11, Javier Ruiz-Martinez12, Elisabet Mondragon12, Eitan Friedman13, Sharon Hassin-Baer11,14, Roy N Alcalay15, Helen Mejia-Santana15, Jan Aasly10, Tatiana Foroud16, Karen Marder15, Nir Giladi4, Susan Bressman2, Rachel Saunders-Pullman2. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. 2. Department of Neurology, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 3. Department of Neurology, University of California San Francisco, San Francisco, California, USA. 4. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. 5. Neurology Service, Hospital Clínic, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat de Barcelona, Catalonia, Spain. 6. Neurology Unit, Hospital General de Granollers, Universitat Internacional de Catalunya, Granollers, Barcelona, Spain. 7. Hertie-Institut für klinische Hirnforschung, Tubingen, Germany. 8. Movement Disorders Unit, Neurology Service, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain. 9. Department of Neurology, Christian-Albrechts-University, Kiel, Germany. 10. Department of Neurology, St. Olavs Hospital, and Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. 11. Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 12. Neurology Department, Donostia University Hospital, Biodonostia Institut Research, Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas, San Sebastian, Gipuzkoa, Spain. 13. The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer and the Departments of Internal Medicine and Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. 14. Parkinson's Disease and Movement Disorders Clinic and Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 15. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. 16. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract
BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. RESULTS: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers.
BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS:Cancer outcomes were compared among 257 LRRK2-PDpatients, 712 IPDpatients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPDpatients. RESULTS: Although cancer prevalence was similar among LRRK2-PDpatients (32.3%), IPDpatients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PDpatients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPDpatients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PDpatients suggest that LRRK2 mutations heighten risks of certain cancers.
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