Chatterjee Srilagna, Paul Nirvika, Das Anwesha, Bank Sarbashri, Bankura Biswabandhu, Sarkar Kunal, Saha Soumen, Malakar Subhajit, Choudhury Sunirmal, Ghosh Sudakshina, Das Madhusudan
Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
Multidisciplinary Research Unit, Calcutta Medical College and Hospital, Kolkata, West Bengal, India.
Urol Oncol. 2025 Jun;43(6):394.e9-394.e22. doi: 10.1016/j.urolonc.2024.12.266. Epub 2025 Jan 13.
Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive malignancy, with the von Hippel-Lindau (VHL) gene playing a critical role in its pathogenesis. However, the association between VHL gene variants and sporadic ccRCC risk remains unexplored in the Indian population. This study aimed to investigate the somatic and germline variants of the VHL gene in sporadic ccRCC patients from West Bengal, India, and their association with disease risk and clinicopathological parameters.
A total of 210 ccRCC patients and 255 ethnicity-matched healthy controls were enrolled. Genomic DNA from blood and tissue samples was analyzed using PCR-based Sanger sequencing. The association of VHL variants with ccRCC risk was assessed using Chi-square tests. The impact of genetic variants on patient clinicopathological features and overall survival was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models.
We identified twenty-three single nucleotide variants (SNVs) in the VHL gene, including 3 novel variants, OR250433 T > G, OR125589 C > T and OQ627404 G > C. The intronic variant rs61758376 G > C and 3'UTR variant rs1642742 A > G were significantly associated with an increased risk of ccRCC (OR = 1.676, P = 0.0074; OR = 1.735, P = 0.0171, respectively). The rs1642742 GG genotype was also significantly associated with larger tumor size (P < 0.05) and advanced tumor stage (pT4). Kaplan-Meier analysis indicated poorer overall survival for patients with the rs1642742 GG genotype (log-rank P = 0.029).
Our study is the first to document the association of VHL gene variants with sporadic ccRCC risk and clinical outcomes in the Indian population. The identified variants, particularly rs61758376 and rs1642742, could serve as potential biomarkers for ccRCC susceptibility and prognosis.
透明细胞肾细胞癌（ccRCC）是一种常见且侵袭性强的恶性肿瘤，冯·希佩尔-林道（VHL）基因在其发病机制中起关键作用。然而，在印度人群中，VHL基因变异与散发性ccRCC风险之间的关联尚未得到探索。本研究旨在调查印度西孟加拉邦散发性ccRCC患者中VHL基因的体细胞和种系变异，以及它们与疾病风险和临床病理参数的关联。
共纳入210例ccRCC患者和255例种族匹配的健康对照。使用基于PCR的桑格测序法分析血液和组织样本中的基因组DNA。使用卡方检验评估VHL变异与ccRCC风险的关联。使用Kaplan-Meier生存分析和Cox比例风险模型评估基因变异对患者临床病理特征和总生存期的影响。
我们在VHL基因中鉴定出23个单核苷酸变异（SNV），包括3个新变异，即OR250433 T>G、OR125589 C>T和OQ627404 G>C。内含子变异rs61758376 G>C和3'UTR变异rs1642742 A>G与ccRCC风险增加显著相关（OR分别为1.676，P=0.0074；OR为1.735，P=0.0171）。rs1642742 GG基因型也与更大的肿瘤大小（P<0.05）和晚期肿瘤分期（pT4）显著相关。Kaplan-Meier分析表明，rs1642742 GG基因型患者的总生存期较差（对数秩检验P=0.029）。
我们的研究首次记录了VHL基因变异与印度人群散发性ccRCC风险及临床结局的关联。所鉴定的变异，特别是rs61758376和rs1642742，可作为ccRCC易感性和预后的潜在生物标志物。
