HTT, ATXN1 and ATXN2 CAG triplet repeat sizes: exploring their role in the disease risk and cancer comorbidity in Parkinson's disease.

IF 4.1 Q1 CLINICAL NEUROLOGY Brain communications Pub Date : 2025-02-06 eCollection Date: 2025-01-01 DOI:10.1093/braincomms/fcaf060

Sergio Pérez-Oliveira, Ignacio Álvarez, Manuel Menéndez-González, Israel David Duarte-Herrera, Marta Blázquez-Estrada, Juan Castilla-Silgado, Esther Suárez, Ciara García-Fernández, Pablo Siso-García, Pablo García-González, Maitee Rosende-Roca, Mercè Boada, Agustín Ruiz, Jon Infante, Beatriz De la Casa-Fages, Isabel González-Aramburu, Victoria Álvarez, Pau Pastor

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Abstract

Parkinson's disease genetic embraces genetic and non-genetic factors. It has been suggested a link between CAG repeat number in the HTT, ATXN1 and ATXN2 genes and different neurodegenerative diseases. Several genetic factors involved in Parkinson's disease development are indeed associated with cancer pathways. Moreover, several studies found a low prevalence of cancer in neurodegenerative diseases that can be associated with a low CAG repeat size in several genes. This study aimed to investigate the influence of CAG repeat sizes in ATXN1, ATXN2 and HTT genes on the risk for developing cancer and Parkinson's disease in a large cohort of patients with idiopathic Parkinson's disease and healthy controls. The work included 1052 patients with idiopathic Parkinson's disease and 1070 controls of European ancestry. CAG repeat sizes in HTT, ATXN1 and ATXN2 genes were analysed. Dunn's multiple comparison test for quantitative variables and logistic and linear regression were used. The long ATXN1 and HTT alleles and CAG size and both the ATXN2 short and long alleles were predictors for the Parkinson's disease risk. The long CAG ATXN1 allele gene was associated with the risk of cancer. No association was observed between CAG size in the HTT and ATXN2 genes and risk of cancer in patients with Parkinson's disease. We described an association of HTT, ATXN1 and ATXN2 with the risk of Parkinson's disease, which reinforce the hypothesis of the common pathway of neurodegeneration. Besides, ATXN1 could be a predictor of cancer risk among patients with Parkinson's disease, and these results suggest that cancer and neurodegeneration processes can share common pathways.