Specific Parkinson’s Gene Mutation Linked to Higher Risk of Leukemia, Colon Cancer, Study Finds

People with Parkinson’s disease who have a specific mutation in the LRRK2 gene may be 10 times more likely to develop leukemia, and twice as likely to have colon cancer, researchers report.

The researchers say this particular patient population should be closely monitored and screened for the early detection of cancer.

These findings, “Cancer Outcomes Among Parkinson’s Disease Patients with Leucine Rich Repeat Kinase 2 Mutations, Idiopathic Parkinson’s Disease Patients, and Nonaffected Controls,” were published in Movement Disorders.

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.

Different studies indicate Parkinson’s patients with a specific mutation in the LRRK2 gene, known as G2019S, have an increased risk of developing certain cancers compared with people with Parkinson’s disease of unknown cause.

“However, it is unclear whether the increased risk among LRRK2-PD [Parkinson’s disease] patients would be observed when compared with unaffected controls who are noncarriers of the G2019S mutation,” the researchers said.

Investigators from the Albert Einstein College of Medicine and Mount Sinai Beth Israel Medical Center sought to compare the prevalence of cancer among Parkinson’s patients with the LRRK2 mutation, people with Parkinson’s of unknown cause (also called idiopathic Parkinson’s), and healthy individuals (controls). To do so, they used a standardized questionnaire across seven international LRRK2 and Parkinson’s-related research centers.

The gathered data was then combined with previously published information to examine the associations between the LRRK2 G2019S mutation and several types of cancer.

Researchers studied the cancer outcomes of 257 LRRK2 G2019S Parkinson’s patients, 712 people with idiopathic Parkinson’s, and 218 genetically unrelated controls, ages 35 or older. On average, the Parkinson’s patients were 68.2 years old, while the control sample was 4 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.

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. Researchers note that only 5 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.

“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,” Ilir Agalliu, MD, PhD, associate professor in the department of epidemiology and population health at Albert Einstein College of Medicine, and first author of the study, said in a press release.