Wei Xi, Qin Rong, Yin Liang, Iqbal Muhammad Asad, Shaibu Zakari, Li Guorui, Wu Ting
Department of Pathology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212000, China.
Department of Medical Oncology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212000, China.
J Cancer Res Clin Oncol. 2025 May 20;151(5):170. doi: 10.1007/s00432-025-06226-6.
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with both genetic and environmental risk factors. The PON1 rs854560 (L55M) polymorphism has been implicated in cancer susceptibility through its role in oxidative stress regulation, but its association with CRC remains unclear, particularly in Asian populations.
This study aimed to investigate the association between the PON1 rs854560 polymorphism and CRC susceptibility in a Chinese cohort, while assessing its impact on PON1 expression and enzymatic activity.
A case-control study was conducted on 1,003 CRC patients and 1,303 healthy controls. The impact of the Pon1-rs854560 SNP was assessed by comparing the genotypes of individuals diagnosed with CRC to those of controls without the disease.
Genotype distribution showed slight differences between the case and control groups. The frequency of the AA genotype was slightly lower in the case group (91.72%) than in the control group (93.71%). The AT genotype was observed at similar frequencies in both groups (8.28% in the case group and 6.14% in the control group). Notably, the TT genotype was absent in the case group but present in 0.15% of the control group. Genotype combination analysis suggested that individuals carrying the AT + TT genotype (8.28%) had a higher susceptibility to CRC compared to those with the AA + AT genotype (100%). Allele frequency analysis revealed a slightly higher frequency of allele T in the case group (8.28%) than in the control group (6.45%). Additionally, lower PON1 mRNA and protein expression were associated with CRC progression, including features such as poorer differentiation, deeper tumor invasion, and vascular, nerve, and lymphatic metastasis.
The PON1 rs854560 polymorphism influences CRC risk in Chinese individuals, likely through reduced PON1 expression and detoxification capacity. These findings highlight its potential as a genetic biomarker for CRC susceptibility and suggest PON1's role in tumor progression. Further studies should validate these associations in diverse populations and explore therapeutic strategies targeting PON1 activity.
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一，存在遗传和环境风险因素。PON1 rs854560（L55M）多态性因其在氧化应激调节中的作用而与癌症易感性有关，但其与结直肠癌的关联仍不明确，尤其是在亚洲人群中。
本研究旨在调查中国队列中PON1 rs854560多态性与结直肠癌易感性之间的关联，同时评估其对PON1表达和酶活性的影响。
对1003例结直肠癌患者和1303例健康对照进行病例对照研究。通过比较被诊断为结直肠癌的个体与无病对照的基因型，评估Pon1-rs854560 SNP的影响。
病例组和对照组的基因型分布存在细微差异。病例组中AA基因型的频率（91.72%）略低于对照组（93.71%）。两组中AT基因型的频率相似（病例组为8.28%，对照组为6.14%）。值得注意 的是，病例组中不存在TT基因型，而对照组中有0.15%存在该基因型。基因型组合分析表明，携带AT + TT基因型的个体（8.28%）比携带AA + AT基因型的个体（100%）患结直肠癌的易感性更高。等位基因频率分析显示，病例组中等位基因T的频率（8.28%）略高于对照组（6.45%）。此外，较低的PON1 mRNA和蛋白表达与结直肠癌进展相关，包括分化较差、肿瘤浸润较深以及血管、神经和淋巴转移等特征。
PON1 rs854560多态性可能通过降低PON1表达和解毒能力影响中国个体患结直肠癌的风险。这些发现突出了其作为结直肠癌易感性遗传生物标志物的潜力，并提示PON1在肿瘤进展中的作用。进一步的研究应在不同人群中验证这些关联，并探索针对PON1活性的治疗策略。
