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癌症相关变化与低至中度接触焊接烟尘:一项纵向研究。

Cancer-related changes and low-to-moderate exposure to welding fumes: A longitudinal study.

机构信息

Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden.

出版信息

Scand J Work Environ Health. 2022 Jan 1;48(1):21-30. doi: 10.5271/sjweh.3988. Epub 2021 Sep 27.

Abstract

OBJECTIVE

This study tested for an association between early cancer-related biomarkers and low-to-moderate exposure to fumes from welding mild steel.

METHODS

Male, non-smoking participants from southern Sweden were recruited and examined (N=338, 171 welders and 167 controls); of these, 78 welders and 96 controls were examined on two occasions six years apart. Exposure to welding fumes was evaluated by measuring respirable dust, welding years, and cumulative exposure. DNA methylation of CpG sites within the cancer-related genes AHRR, F2RL3, and B3GNTL1 was measured by pyrosequencing and relative mitochondrial DNA copy number and telomere length were measured by qPCR in whole-blood samples. Multivariate models were used for longitudinal analysis.

RESULTS

Median exposure to respirable dust was 0.7 mg/m at both timepoints, adjusted for use of personal protective equipment. Compared with controls, welders showed a significant decrease over time in DNA methylation of B3GNTL1 CpG1 and CpG4 [adjusted for age, body mass index, and smoking: β=-0.66, standard error (SE)=0.28; β=-0.48, SE=0.24, respectively]. In addition, exposure to respirable dust and cumulative exposure was associated with a decrease in methylation of F2RL3 CpG2 among all welders (adjusted β=-0.67, SE=0.23 and β=-0.03, SE=0.02, respectively). No significant associations were found for AHRR, mitochondrial DNA copy number, or telomere length.

CONCLUSION

Low-to-moderate exposure to welding fumes was associated with a small effect on selected early epigenetic biomarkers of cancer. The direction of the methylation pattern (lower methylation of specific CpG sites) indicates early lung cancer-related changes associated with mild steel welding.

摘要

目的

本研究旨在检验与低至中度接触焊接软钢产生的烟雾相关的早期癌症相关生物标志物与癌症的关联性。

方法

从瑞典南部招募了男性非吸烟参与者进行检查(N=338,171 名焊工和 167 名对照者;其中 78 名焊工和 96 名对照者在六年后两次进行了检查)。通过测量可吸入粉尘、焊接年限和累计暴露量来评估焊接烟尘暴露情况。通过焦磷酸测序测量与癌症相关基因 AHRR、F2RL3 和 B3GNTL1 内 CpG 位点的 DNA 甲基化水平,并通过 qPCR 测量全血样本中的相对线粒体 DNA 拷贝数和端粒长度。使用多变量模型进行纵向分析。

结果

两次检测时,可吸入粉尘的中位数暴露水平均为 0.7mg/m,调整了个人防护设备的使用情况。与对照组相比,焊工的 B3GNTL1 CpG1 和 CpG4 的 DNA 甲基化水平随时间呈显著下降趋势[调整年龄、体重指数和吸烟因素后:β=-0.66,标准误(SE)=0.28;β=-0.48,SE=0.24]。此外,所有焊工的 F2RL3 CpG2 甲基化水平与可吸入粉尘暴露和累计暴露均呈负相关(调整后β=-0.67,SE=0.23 和β=-0.03,SE=0.02)。未发现 AHRR、线粒体 DNA 拷贝数或端粒长度的显著相关性。

结论

低至中度接触焊接烟尘与特定癌症早期表观遗传生物标志物的微小变化相关。特定 CpG 位点的低甲基化模式表明与软钢焊接相关的早期肺癌变化。

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