Genomic instability in ovarian cancer: Through the lens of single nucleotide polymorphisms

• Published in: Clinica chimica acta 2025-01, Vol.565, p.119992, Article 119992
• Main Authors: Canchi Sistla, Harshavardhani, Talluri, Srikanth, Rajagopal, Taruna, Venkatabalasubramanian, Sivaramakrishnan, Rao Dunna, Nageswara
• Format: Article
• Language: English
• Subjects: Apoptotic genes; Case-control studies; Cell cycle genes; DNA damage response; DNA repair genes; Female; Genetic variants; Genomic Instability; Humans; in silico tools; Ovarian cancer; Ovarian Neoplasms - genetics; Polymorphism, Single Nucleotide; Single nucleotide polymorphisms; Telomerase maintenance genes
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2024.119992

•The review provides an in-depth analysis of polymorphisms in genes of the pathways that maintain genome stability, viz., DNA damage response, repair, cell cycle, apoptosis, and telomere maintenance, and discusses their implications in ovarian carcinogenesis.•The review also intersects with fields such as bioinformatics, broadening its relevance and use of computational tools and providing a detailed analysis of genetic association studies like case-control studies and meta-analyses.•It highlights the research gaps in studying these caretaker gene variants and includes novel perspectives to overcome the current challenges in SNP-based studies. Ovarian cancer (OC) is the deadliest gynecological malignancy among all female reproductive cancers. It is characterized by high mortality rate and poor prognosis. Genomic instability caused by mutations, single nucleotide polymorphisms (SNPs), copy number variations (CNVs), microsatellite instability (MSI), and chromosomal instability (CIN) are associated with OC predisposition. SNPs, which are highly prevalent in the general population, show a greater relative risk contribution, particularly in sporadic cancers. Understanding OC etiology in terms of genetic basis can increase the use of molecular diagnostics and provide promising approaches for designing novel treatment modalities. This will help deliver personalized medicine to OC patients, which may soon be within reach. Given the pivotal impact of SNPs in cancers, the primary emphasis of this review is to shed light on their prevalence in key caretaker genes that closely monitor genomic integrity, viz., DNA damage response, repair, cell cycle checkpoints, telomerase maintenance, and apoptosis and their clinical implications in OC. We highlight the current challenges faced in different SNP-based studies. Various computational methods and bioinformatic tools employed to predict the functional impact of SNPs have also been comprehensively reviewed concerning OC research. Overall, this review identifies that variants in the DDR and HRR pathways are the most studied, implying their critical role in the disease. Conversely, variants in other pathways, such as NHEJ, MMR, cell cycle, apoptosis, telomere maintenance, and PARP genes, have been explored the least.