Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression

• Published in: International journal of environmental research and public health Vol. 19; no. 19; p. 12471
• Main Authors: Chang, Chi-Fen, Huang, Shu-Pin, Hsueh, Yu-Mei, Geng, Jiun-Hung, Huang, Chao-Yuan, Bao, Bo-Ying
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.09.2022; MDPI
• Subjects: Alleles; Alzheimer's disease; Bioinformatics; Biomarkers; Carcinoma, Renal Cell - genetics; Cell adhesion & migration; Datasets; Diabetes; Gene expression; Genes; Genetic analysis; Genetic diversity; Genetic Testing; Genetic variance; Genomes; Health risk assessment; Hospitals; Humans; Hypertension; Intracellular signalling; Kidney cancer; Kidney Neoplasms - genetics; Medical prognosis; Nerve Tissue Proteins - genetics; Patients; Polymorphism, Single Nucleotide; Proteins; Regression analysis; Risk analysis; Risk factors; Statistical analysis; Survival; Synaptic transmission; United States > US; Taiwan; renal cell carcinoma; SHANK; risk; single-nucleotide polymorphism; survival
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph191912471

SH3 and multiple ankyrin repeat domains (SHANK) is a family of scaffold proteins that were first identified to be involved in balancing synaptic transmission via regulation of intracellular signalling crosstalk and have been linked to various cancers. However, the role of the SHANK genes in renal cell carcinoma (RCC) remains to be elucidated. In this study, we aimed to evaluate whether genetic variants in SHANK family genes affect the risk of RCC and survival of patients. A genetic association study was conducted using logistic regression and Cox regression analyses, followed by the correction for a false discovery rate (FDR), in 630 patients with RCC and controls. A pooled analysis was further performed to summarise the clinical relevance of gene expression in RCC. After adjustment for known risk factors and the FDR, the rs10792565 T allele was found to be associated with an increased risk of RCC (adjusted odds ratio = 1.79, 95% confidence interval = 1.32-2.44, = 1.96 × 10 , = 0.030), whereas no significant association was found with RCC survival. A pooled analysis of 19 independent studies, comprising 1509 RCC and 414 adjacent normal tissues, showed that the expression of was significantly lower in RCC than in normal tissues ( < 0.001). Furthermore, low expression of was correlated with an advanced stage and poor prognosis for patients with clear cell and papillary RCC. This study suggests that rs10792565 is associated with an increased risk of RCC and that may play a role in RCC progression.