Background:

Lung cancer is the leading cause of cancer-related deaths worldwide. Copy number variation (CNV) in several genetic regions correlate with cancer susceptibility. Hence, this study evaluated the association between CNV and non-small cell lung cancer (NSCLC) in the peripheral blood.

Methods:

Blood samples of 150 patients with NSCLC and 150 normal controls were obtained from a bioresource center (Seoul, Korea). Through an epigenome-wide analysis using the MethylationEPIC BeadChip method, we extracted CNVs by using an SVS8 software-supplied multivariate method. We compared CNV frequencies between the NSCLC and controls, and then performed stratification analyses according to smoking status.

Results:

We acquired 979 CNVs, with 582 and 967 copy-number gains and losses, respectively. We identified five nominally significant associations (ACOT1, NAA60, GSDMD, HLA-DPA1, and SLC35B3 genes). Among the current smokers, the NSCLC group had more CNV losses and gains at the GSDMD gene in chromosome 8 (P=0.02) and at the ACOT1 gene in chromosome 14 (P=0.03) than the control group. It also had more CNV losses at the NAA60 gene in chromosome 16 (P=0.03) among non-smokers. In the NSCLC group, current smokers had more CNV gains and losses at the ACOT1 gene in chromosome 14 (P=0.003) and at HLA-DPA1 gene in chromosome 6 (P=0.02), respectively, than non-smokers.

Conclusion:

Five nominally significant associations were found between the NSCLC and CNVs. CNVs are associated with the mechanism of lung cancer development. However, the role of CNVs in lung cancer development needs further investigation.

中文翻译：

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肺癌患者血液中拷贝数变异的差异

背景：

肺癌是全球癌症相关死亡的主要原因。几个遗传区域中的拷贝数变异 (CNV) 与癌症易感性相关。因此，本研究评估了外周血中 CNV 与非小细胞肺癌 (NSCLC) 之间的关联。

方法：

来自生物资源中心（韩国首尔）的 150 名 NSCLC 患者和 150 名正常对照的血样。通过使用 MethylationEPIC BeadChip 方法进行的表观基因组分析，我们使用 SVS8 软件提供的多变量方法提取了 CNV。我们比较了 NSCLC 和对照组之间的 CNV 频率，然后根据吸烟状况进行分层分析。

结果：

我们收购了 979 个 CNV，分别有 582 和 967 个拷贝数的收益和损失。我们确定了五个名义上显着的关联（ACOT1、NAA60、GSDMD、HLA-DPA1 和 SLC35B3 基因）。目前吸烟人群中，NSCLC组8号染色体GSDMD基因（P =0.02）和14号染色体ACOT1基因（P =0.03）CNV损失和增加明显高于对照组。在非吸烟者中，16 号染色体 NAA60 基因的 CNV 损失也更多（P = 0.03）。在 NSCLC 组中，目前吸烟者在 14 号染色体的 ACOT1 基因（P = 0.003）和 6 号染色体的 HLA-DPA1 基因（P = 0.02）处的 CNV 增益和损失分别高于非吸烟者。

结论：

在 NSCLC 和 CNV 之间发现了五个名义上显着的关联。CNVs与肺癌发生的机制有关。然而，CNVs 在肺癌发展中的作用需要进一步研究。