Jia Zhuoqi, Zhou Weiru, Zhang Guangjian, Fu Junke, Li Daxu, Ren Le
Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Nuclear Medicine, Xi'an Gaoxin Hospital, Xi'an 710075, Shaanxi, China.
Genomics. 2020 Sep;112(5):3465-3472. doi: 10.1016/j.ygeno.2020.05.023. Epub 2020 May 25.
Lung cancer (LC) is one of the fastest-growing malignant tumors in the world in terms of morbidity and mortality. CYP3A4 plays a crucial role in the occurrence of LC. Little is known about the contribution of CYP3A4 polymorphisms for non-small cell lung cancer (NSCLC) risk. This study aimed to explore the correlation of CYP3A4 genetic variants (rs3735451, rs4646440, rs35564277, and rs4646437) with NSCLC risk.
Four single nucleotide polymorphisms (SNPs) were genotyped by Agena MassARRAY in this case-control study (507 NSCLC patients and 505 controls) among a Shaanxi Han population. Hardy-Weinberg equilibrium (HWE) of each SNP in controls was evaluated by exact test. The association of CYP3A4 polymorphisms with NSCLC risk was explored by calculating odds ratios (OR) and 95% confidence intervals (CI) using logistic regression analysis with adjustment for age and gender.
Our research revealed that rs4646440 was significantly associated with an increased risk of NSCLC (OR 2.64, p = .005), while rs4646437 played a protective role in NSCLC risk (OR 0.48, p = 4.00 × 10). Stratified analyses indicated that rs4646440 significantly enhanced the susceptibility of NSCLC in BMI > 24 kg/m, non-smokers and non-drinkers (OR 14.29, p = .012; OR 1.56, p = .023; OR 1.67, p = .031, respectively). Besides, we observed that rs3735451 exhibited an increased risk of NSCLC in BMI > 24 kg/m (OR 2.47, p = .030), whereas rs4646437 had a reduced risk of NSCLC in BMI ≤ 24 kg/m (OR 0.47, p = 5.17 × 10). We also found that rs35564277 was considered as a protective factor of NSCLC in non-smokers (OR 0.50, p = .032).
Our study indicated that CYP3A4 genetic variants were associated with NSCLC susceptibility in a Shaanxi Han population.
肺癌(LC)是世界上发病率和死亡率增长最快的恶性肿瘤之一。细胞色素P450 3A4(CYP3A4)在肺癌的发生中起关键作用。关于CYP3A4基因多态性对非小细胞肺癌(NSCLC)风险的影响知之甚少。本研究旨在探讨CYP3A4基因变异(rs3735451、rs4646440、rs35564277和rs4646437)与NSCLC风险的相关性。
在这项病例对照研究中,对陕西汉族人群中的507例NSCLC患者和505例对照,采用Agena MassARRAY技术对4个单核苷酸多态性(SNP)进行基因分型。通过精确检验评估对照组中每个SNP的哈迪-温伯格平衡(HWE)。采用逻辑回归分析并调整年龄和性别,计算比值比(OR)和95%置信区间(CI),以探讨CYP3A4基因多态性与NSCLC风险的关联。
我们的研究表明,rs4646440与NSCLC风险增加显著相关(OR 2.64,p = 0.005),而rs4646437对NSCLC风险起保护作用(OR 0.48,p = 4.00×10)。分层分析表明,rs4646440在体重指数(BMI)>24 kg/m²、不吸烟者和不饮酒者中显著增强了NSCLC的易感性(分别为OR 14.29,p = 0.012;OR 1.56,p = 0.023;OR 1.67,p = 0.031)。此外,我们观察到rs3735451在BMI>24 kg/m²时显示出NSCLC风险增加(OR 2.47,p = 0.030),而rs4646437在BMI≤24 kg/m²时NSCLC风险降低(OR 0.47,p = 5.17×10)。我们还发现rs35564277在不吸烟者中被认为是NSCLC的保护因素(OR 0.50,p = 0.032)。
我们的研究表明,CYP3A4基因变异与陕西汉族人群的NSCLC易感性相关。