Paraoxonase 1 polymorphisms and their relationship with gastric cancer risk: a biochemical perspective on oxidative stress.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.