Oxidative Stress-Related KEAP1 and NRF2 Genes Contributed to the Risk of Epithelial Ovarian Cancer.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2025-02-13 DOI:10.1007/s10528-025-11044-z

Xiaoqian Tong, Xiaoli Zhu, Xila Wang, Yanlin Xu, Pei Huang, Leiqing Zhou, Yanxiang Ji, Lifang Wu

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引用次数: 0

Abstract

The NRF2/KEAP1 signaling pathway, crucial for cellular defense against oxidative stress, may influence epithelial ovarian cancer (EOC) risk. This study investigates the association between KEAP1 gene polymorphisms and EOC risk in Han Chinese individuals, while exploring correlations between these genetic variants and serum levels of KEAP1 and NRF2 proteins. We conducted a case-control study involving 1962 EOC patients and 2057 controls, genotyping ten tag single-nucleotide polymorphisms (SNPs) in KEAP1. Serum KEAP1 and NRF2 levels were measured using ELISA. Genetic association analyses and ANOVA were employed to assess relationships between SNPs, EOC risk, and serum protein levels. Notably, only SNP rs3177696 in KEAP1 showed a significant association with EOC risk. The G allele of rs3177696 conferred a protective effect against EOC (OR [95% CI] = 0.58 [0.47-0.72], P = 2.91 × 10^-7). Furthermore, rs3177696 genotypes were significantly associated with serum levels of both KEAP1 and NRF2, as well as their ratio. EOC patients carrying GG, AG, and AA genotypes exhibited mean serum KEAP1 levels of 2.46, 2.16, and 2.04 (P = 2.43 × 10^-9), respectively. Conversely, serum NRF2 levels decreased with increasing G allele copies (GG: 4.58, AG: 4.95, AA: 5.02; P = 0.0002). This study provides compelling evidence linking EOC risk to the oxidative stress-related gene KEAP1, with the G allele of rs3177696 demonstrating a protective effect. These findings suggest a potential role for the NRF2/KEAP1 pathway in EOC pathogenesis and highlight promising avenues for future research in EOC prevention and treatment strategies.

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.