膀胱癌（BC）是泌尿系统严重的健康问题，其特点是高复发风险。根据最近的GLOBOCAN报告，膀胱癌在全球被诊断出的癌症中占3％，在常见癌症列表中排名第十位。尽管有大量的研究，但膀胱癌发展的完整机制仍然不明。然而，宝贵的结果表明氧化应激在膀胱癌发展中起着关键作用。因此，本研究探讨了c. 47 C>T (rs4880)-SOD2，c. 1823 C>T (rs2297518)和g.-1026 C>A (rs2779249)-NOS2(iNOS)多态性是否与膀胱癌的发生相关，以及膀胱癌是否导致外周血单个核细胞（PBMCs）中SOD2和NOS2表达和甲基化状态的改变。为实现此目标，使用TaqMan SNP基因分型测定试剂盒、TaqMan基因表达测定试剂盒和甲基化敏感高分辨熔解技术，分别用于基因分型分析、基因表达评估和启动子甲基化状态评估。我们的研究结果证实，g.-1026 C>A单核苷酸多态性的杂合子与膀胱癌的发生风险降低相关。此外，我们检测到膀胱癌的发展影响了PBMCs中被研究基因的启动子区域的表达水平和甲基化状态。总之，我们的研究结果证实了氧化应激，尤其是NOS2多态性以及SOD2和NOS2启动子的表达和甲基化状态的改变参与了膀胱细胞癌症转化起始过程。©2023. Springer Nature Limited.

Bladder cancer (BC) is a severe health problem of the genitourinary system and is characterised by a high risk of recurrence. According to the recent GLOBOCAN report, bladder cancer accounts for 3% of diagnosed cancers in the world, taking 10th place on the list of the most common cancers. Despite numerous studies, the full mechanism of BC development remains unknown. Nevertheless, precious results suggest a crucial role of oxidative stress in the development of BC. Therefore, this study explores whether the c. 47 C > T (rs4880)-SOD2, (c. 1823 C > T (rs2297518) and g.-1026 C > A (rs2779249)-NOS2(iNOS) polymorphisms are associated with BC occurrence and whether the bladder carcinogenesis induces changes in SOD2 and NOS2 expression and methylation status in peripheral blood mononuclear cells (PBMCs). In this aim, the TaqMan SNP genotyping assay, TaqMan Gene Expression Assay, and methylation-sensitive high-resolution melting techniques were used to genotype profiling and evaluate the expression of the genes and the methylation status of their promoters, respectively. Our findings confirm that heterozygote of the g.-1026 C > A SNP was associated with a decreased risk of BC. Moreover, we detected that BC development influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs. Concluding, our results confirmed that oxidative stress, especially NOS2 polymorphisms and changes in the expression and methylation of the promoters of SOD2 and NOS2 are involved in the cancer transformation initiation of the cell urinary bladder.© 2023. Springer Nature Limited.