Department of Oncology, Beijing Hospital, China Ministry of Health, Beijing, PR China.
J Investig Med. 2012 Mar;60(3):592-7. doi: 10.2310/JIM.0b013e318245d557.
Oxidative stress and free radicals have been indicated to be associated with increased risk of various cancers. Paraoxonase 1 (PON1) gene, encoding PON1 protein, plays an important role as an endogenous free-radical scavenging molecule. The aim of the present study was to determine whether genetic polymorphisms of the PON1 gene are associated with the risk and prognosis of non-small cell lung cancer (NSCLC).
A total of 356 patients with NSCLC and 184 healthy controls were enrolled in this study. Q192R and L55M polymorphisms of the PON1 gene were genotyped using polymerase chain reaction and restriction fragment length polymorphism method.
As for the Q192R polymorphism, the patients with NSCLC showed higher frequencies of QR and RR genotypes than the normal controls. Unconditional logistic regression analysis revealed that QR and RR genotypes were significantly associated with the presence of NSCLC compared with the QQ genotype. No significant differences were found in the genotypes of the L55M polymorphism between the patients with NSCLC and the healthy controls. The QR and RR genotypes were significantly associated with TNM stage and nodal metastasis. Survival analysis indicated that the patients with NSCLC with the QR and RR genotypes had poorer disease-free survival than those with the QQ genotype (P=0.011). Multivariable Cox regression analysis revealed that QR and RR genotypes were an independent factor for the prognosis of NSCLC (hazard ratio, 1.505; 95% confidence interval, 1.004-2.256; P=0.048).
The Q192R polymorphism of the PON1 gene may be associated with the risk and prognosis of NSCLC in a Chinese Han population.
氧化应激和自由基已被表明与各种癌症的风险增加有关。 对氧磷酶 1（PON1）基因，编码 PON1 蛋白，作为一种内源性自由基清除分子发挥着重要作用。本研究旨在确定 PON1 基因的遗传多态性是否与非小细胞肺癌（NSCLC）的风险和预后相关。
本研究共纳入 356 例 NSCLC 患者和 184 例健康对照者。采用聚合酶链反应和限制性片段长度多态性方法检测 PON1 基因的 Q192R 和 L55M 多态性。
对于 Q192R 多态性，与正常对照组相比，NSCLC 患者的 QR 和 RR 基因型频率更高。非条件逻辑回归分析显示，与 QQ 基因型相比，QR 和 RR 基因型与 NSCLC 的存在显著相关。PON1 基因 L55M 多态性的基因型在 NSCLC 患者和健康对照组之间无显著差异。QR 和 RR 基因型与 TNM 分期和淋巴结转移显著相关。生存分析表明，QR 和 RR 基因型的 NSCLC 患者无病生存时间明显短于 QQ 基因型患者（P=0.011）。多变量 Cox 回归分析显示，QR 和 RR 基因型是非小细胞肺癌预后的独立因素（危险比，1.505；95%置信区间，1.004-2.256；P=0.048）。
PON1 基因的 Q192R 多态性可能与中国汉族人群 NSCLC 的风险和预后相关。
