Purpose

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.

Methods

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.

Results

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 × 10⁻⁷). Stratified analyses indicated that rs4646440 significantly enhanced the susceptibility of NSCLC in BMI > 24 kg/m², 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/m² (OR 2.47, p = .030), whereas rs4646437 had a reduced risk of NSCLC in BMI ≤ 24 kg/m² (OR 0.47, p = 5.17 × 10⁻⁵). We also found that rs35564277 was considered as a protective factor of NSCLC in non-smokers (OR 0.50, p = .032).

Conclusion

Our study indicated that CYP3A4 genetic variants were associated with NSCLC susceptibility in a Shaanxi Han population.

中文翻译：

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CYP3A4 基因变异与陕西汉族非小细胞肺癌的易感性有关。

目的

就发病率和死亡率而言，肺癌（LC）是世界上增长最快的恶性肿瘤之一。CYP3A4在LC的发生中起关键作用。关于CYP3A4多态性对非小细胞肺癌 (NSCLC) 风险的贡献知之甚少。本研究旨在探讨CYP3A4遗传变异（rs3735451、rs4646440、rs35564277 和 rs4646437）与 NSCLC 风险的相关性。

方法

在该病例对照研究（507 名 NSCLC 患者和 505 名对照）中，在陕西汉族人群中，Agena MassARRAY 对四个单核苷酸多态性 (SNP) 进行了基因分型。对照中每个 SNP 的 Hardy-Weinberg 平衡 (HWE) 通过精确检验进行评估。CYP3A4多态性与 NSCLC 风险的关联是通过使用逻辑回归分析计算比值比 (OR) 和 95% 置信区间 (CI) 并调整年龄和性别来探索的。

结果

我们的研究表明，rs4646440 与 NSCLC 风险增加显着相关（OR 2.64，p  = .005），而 rs4646437 在 NSCLC 风险中发挥保护作用（OR 0.48，p  = 4.00 × 10 ^-7）。分层分析表明，rs4646440 可显着提高 BMI > 24 kg/m ²、非吸烟者和非饮酒者对 NSCLC 的易感性（OR 14.29，p  = .012；OR 1.56，p  = .023；OR 1.67，p  = . 031）。此外，我们观察到 rs3735451 在 BMI > 24 kg/m ^{2 时}表现出增加的 NSCLC 风险（OR 2.47，p  = .030），而 rs4646437 在 BMI ≤ 24 kg/m ^{2 时}降低非小细胞肺癌的风险（OR 0.47，p  = 5.17 × 10 ^-5）。我们还发现 rs35564277 被认为是非吸烟者 NSCLC 的保护因素（OR 0.50，p  = .032）。

结论

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。