medwireNews: Researchers have found that patients with Parkinson disease (PD) who carry mutations in LRRK2 may be more susceptible to certain cancers than their peers without this genetic mutation.
The findings were presented at the EAN Congress 2025 in Helsinki, Finland, by Giulia Di Rauso, from the University of Modena and Reggio Emilia in Italy.
She told delegates that “pathogenic variants in the LRRK2 gene are the most common cause of autosomal dominant monogenic Parkinson’s disease,” and that some epidemiologic, in vitro and mouse model studies have suggested links between variants of the gene and the risk for malignancies and tumorigenesis.
To investigate this further, Di Rauso and colleagues compared the prevalence of malignancies in 519 patients with PD, who had been previously screened for the LRRK2 gene using next-generation sequencing and multiplex ligation-dependent probe amplification.
In all, 42 of the patients had mutated LRRK2 genotypes and 477 had the wild-type LRRK2 genotype. The mean ages of the patients were 62 and 66 years, respectively, and the proportion of men in each group was a corresponding 50% and 63%.
Retrospectively collected data on each individual’s history of malignancies showed that “mutated LRRK2-PD patients had a significantly greater prevalence of oncological disease compared to wild-type LRRK2-PD patients,” said the presenter.
The rates of cancer were 33% versus 19%, respectively, with a total of 26 tumors identified in the PD patients with mutated LRRK2. Of these, cutaneous melanomas were the most prevalent, at 19%, followed by breast cancer, at 15%, hematolymphopoietic system and uterine cancers, at 12% each, and prostate cancer, at 8%.
Di Rauso noted that most of the PD patients with mutated LRRK2 who had cancer carried the G2019S variant, which she explained, increases kinase activity in the LRRK2 protein, and contributes to dopaminergic neuronal damage.
She also pointed out that kinases are “involved in homeostasis of virtually every cellular process,” as well as regulating “nearly every signal transduction cascade.”
The presenter acknowledged the limitations of the small sample size and the fact that there was no comparison with the general population.
Nevertheless, she said that “the study suggests that mutated LRRK2-PD patients may be more susceptible to specific malignancies compared to PD patients without LRRK2 mutations.”
Di Rauso concluded that “if confirmed, the management of these patients could be enhanced by providing not only follow-up care for PD, but also early malignancy screening.”
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