Cava Claudia, Castiglioni Isabella
Department of Science, Technology, and Society, University School for Advanced Studies IUSS Pavia, Palazzo del Broletto, Piazza della Vittoria 15, 27100, Pavia, Italy.
Department of Physics "Giuseppe Occhialini", University of Milan-Bicocca, Piazza dell'Ateneo Nuovo, 20126, Milan, Italy.
Curr Alzheimer Res. 2025;22(3):232-246. doi: 10.2174/0115672050389561250429112631.
Previous studies have shown a correlation between neurodegenerative diseases and cancers. However, the biological processes for these diseases are not completely known, and the genetic factors for their onset are not defined.
This study reports the genetic relationships of different neurodegenerative diseases, such as Multiple Sclerosis (MS), Alzheimer's Disease (AD), and Parkinson's disease (PD) and cancer types (squamous cell lung carcinoma, esophageal adenocarcinoma, and colorectal cancer), with other human traits, based on cross-trait Linkage Disequilibrium Score regression (LDSC). We then applied a clumping approach to select candidate genes for each disease, and via an miRNA analysis, we identified miRNAs that could regulate those genes.
LDSC revealed an inverse association of human traits with neurodegenerative diseases and cancer. Indeed, the cancer types studied were positively correlated with "Body Mass Index (BMI)," while AD, PD, and MS showed a negative correlation. miR-1-3p, miR-34a-5p, and miR-27a-3p were revealed as common biomarkers among the different pathological conditions.
The present study suggests novel genetic associations between neurological diseases, cancer types and new targets to explain the genetic sharing between the diseases.
先前的研究表明神经退行性疾病与癌症之间存在关联。然而,这些疾病的生物学过程尚未完全明确,其发病的遗传因素也未确定。
本研究基于跨性状连锁不平衡评分回归(LDSC)报告了不同神经退行性疾病,如多发性硬化症(MS)、阿尔茨海默病(AD)和帕金森病(PD)以及癌症类型(肺鳞状细胞癌、食管腺癌和结直肠癌)与其他人类性状之间的遗传关系。然后,我们应用聚类方法为每种疾病选择候选基因,并通过miRNA分析,鉴定出可调控这些基因的miRNA。
LDSC显示人类性状与神经退行性疾病和癌症呈负相关。事实上,所研究的癌症类型与“体重指数(BMI)”呈正相关,而AD、PD和MS则呈负相关。miR-1-3p、miR-34a-5p和miR-27a-3p被揭示为不同病理状况下的常见生物标志物。
本研究表明神经疾病、癌症类型之间存在新的遗传关联以及新的靶点,以解释这些疾病之间的遗传共享。