Parkinson’s Gene Mutation Linked to Higher Risk of Leukemia

Parkinson's disease is a progressive nervous system disorder that affects movement. Symptoms start gradually, sometimes starting with a barely noticeable tremor in just one hand. Tremors are common, but the disorder also commonly causes stiffness or slowing of movement.

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are one of the most commonly known genetic causes of Parkinson’s disease. They usually result in the malfunctioning of lysosomes, special compartments within cells that digest and recycle different types of molecules. Lysosomal dysfunction is involved in the formation of Lewy body protein aggregates and, therefore, neurodegeneration.

A large team of scientists collaborating with the Albert Einstein College of Medicine (Bronx, NY, USA) sought to compare the prevalence of cancer among Parkinson’s patients (PD) with the LRRK2 mutation, people with Parkinson’s of unknown cause (also called idiopathic Parkinson’s, IPD), and healthy individuals (controls). To do so, they used a standardized questionnaire across seven international LRRK2 and Parkinson’s-related centers. Cancer outcomes were compared among 257 LRRK2‐PD patients, 712 IPD patients, and 218 controls recruited from seven 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 1,946 IPD patients.

On average, the Parkinson’s patients were 68.2 years old, while the control sample was four years younger, with a mean age of 64 years. Around 77% of study subjects were Ashkenazi Jews, who more commonly carry genetic mutations linked to Parkinson’s, such as LRRK2. The scientists reported that results showed there were no significant differences in the cancer rates of all three study groups. In fact, the rates were similar: 32.3% for LRRK2 G2019S Parkinson’s patients, 27.5% for idiopathic Parkinson’s, and 27.5% for controls.

Nevertheless, individuals with the LRRK2 G2019S mutation had a 4.6-fold increased risk of developing leukemia, and a 1.6-fold higher risk of developing skin cancer. The team noted that only five of the 257 people with LRRK2 G2019S Parkinson’s developed leukemia, compared with no cases in the idiopathic Parkinson’s group. Further analysis also suggested higher risks for colon and kidney cancers in LRRK2 G2019S Parkinson’s, but statistical significance was not attained.

Scientists then combined this data with that of a previous study, which led to an overall study pool totaling 401 people with LRRK2 G2019S Parkinson’s and 1,946 individuals with the idiopathic form of the neurodegenerative disorder. The pooled analysis revealed that individuals with LRRK2 G2019S were 9.84 times more likely to develop leukemia, and 2.34 times more likely to develop colon cancer, in comparison with idiopathic Parkinson’s patients. These findings indicate the LRRK2 G2019 mutation might be associated with the development of several types of cancer.

Ilir Agalliu, MD, PhD, an associate professor and first author of the study, said, “We might consider that if someone is a carrier of the LRRK2 G2019S mutation they should be closely monitored for Parkinson’s and for certain cancers.” The study was published in the September 2019 issue of the journal Movement Disorders.

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