Najafi Elaheh, Pourfarzi Farhad, Mazani Mohammad, Yazdanbod Abbas, Rezagholizadeh Kosar, Fazaeli Aliakbar
Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Mol Biol Rep. 2025 May 21;52(1):472. doi: 10.1007/s11033-025-10563-7.
Gastric cancer (GC) is a significant global health issue, with oxidative stress playing a pivotal role in its pathogenesis. Paraoxonase 1 (PON1), an enzyme with antioxidant properties, may modulate oxidative stress and cancer susceptibility. This study examined the association between two PON1 polymorphisms, rs662 (Q192R) and rs854560 (L55M), and their effects on GC risk and oxidative stress markers.
The study included 250 histopathologically confirmed GC patients and 210 healthy controls. PON1 polymorphisms were genotyped, and biochemical markers-including PON1 and arylesterase (ARE) activities, total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)-were quantified.
The genotype frequencies of rs854560 and rs662 differed significantly between GC patients and controls. The rs854560 polymorphism was linked to GC risk in co-dominant and dominant inheritance models, while rs662 was associated in co-dominant, dominant, and recessive models. PON1 and ARE activities were significantly reduced in GC patients compared to controls (p = 0.001 and p < 0.001, respectively). TAC was higher in controls (p = 0.006), whereas TOS and OSI showed non-significant trends toward elevation in the GC group (p = 0.093 and p = 0.181, respectively). Genotype stratification revealed significant variations in PON1, ARE, TAC, TOS, and OSI levels across rs854560 and rs662 variants.
Our findings indicate that genetic polymorphisms in PON1, specifically rs662 and rs854560, influence susceptibility to gastric cancer by altering oxidative stress markers. These findings provide insights into how PON1 genetic variations affect oxidative stress and contribute to cancer risk.
胃癌（GC）是一个重大的全球健康问题，氧化应激在其发病机制中起关键作用。对氧磷酶1（PON1）是一种具有抗氧化特性的酶，可能调节氧化应激和癌症易感性。本研究检测了两种PON1基因多态性，即rs662（Q192R）和rs854560（L55M）之间的关联，以及它们对胃癌风险和氧化应激标志物的影响。
该研究纳入了250例经组织病理学确诊的胃癌患者和210例健康对照。对PON1基因多态性进行基因分型，并对包括PON1和芳基酯酶（ARE）活性、总抗氧化能力（TAC）、总氧化状态（TOS）和氧化应激指数（OSI）在内的生化标志物进行定量分析。
rs854560和rs662的基因型频率在胃癌患者和对照之间存在显著差异。rs854560多态性在共显性和显性遗传模型中与胃癌风险相关，而rs662在共显性、显性和隐性模型中均有关联。与对照相比，胃癌患者的PON1和ARE活性显著降低（分别为p = 0.001和p < 0.001）。对照组的TAC较高（p = 0.006），而胃癌组的TOS和OSI有升高的趋势，但无统计学意义（分别为p = 0.093和p = 0.181）。基因型分层显示，rs854560和rs662变异的PON1、ARE、TAC、TOS和OSI水平存在显著差异。
我们的研究结果表明，PON1基因多态性，特别是rs662和rs854560，通过改变氧化应激标志物影响胃癌易感性。这些发现为PON1基因变异如何影响氧化应激并导致癌症风险提供了见解。
