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白细胞 DNA 中 AHRR(cg05575921)甲基化程度与肺癌生存。

AHRR (cg05575921) methylation extent of leukocyte DNA and lung cancer survival.

机构信息

Department of Technology, Faculty of Health and Technology, University College Copenhagen, Copenhagen, Denmark.

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

PLoS One. 2019 Feb 7;14(2):e0211745. doi: 10.1371/journal.pone.0211745. eCollection 2019.

Abstract

BACKGROUND

Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.

METHODS

In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation.

RESULTS

We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.

CONCLUSION

AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.

摘要

背景

先前的研究表明,AHRR(cg05575921)低甲基化可能是吸烟、肺癌风险和潜在肺癌生存(在某些肺癌亚型中)的标志物。目前尚不清楚 AHRR(cg05575921)低甲基化是否与肺癌患者的生存降低有关。

方法

在来自哥本哈根前瞻性肺癌研究的 465 名肺癌患者的经亚硫酸氢盐处理的白细胞 DNA 中,我们测量了 AHRR(cg05575921)甲基化。在最大随访 4.4 年期间,380 人死亡。使用 Cox 比例风险模型分析 AHRR(cg05575921)甲基化作为生存功能的函数。

结果

我们观察到累积吸烟与 AHRR 甲基化之间存在预期的反比关系,因为每包年的甲基化(%)降低(系数-0.03;95%置信区间,-0.04 至-0.02,p = 8.6x10-15)。累积吸烟>60 包年与生存降低相关(危险比和 95%置信区间为 1.48;1.05-2.09),然而,当调整性别、体重指数、吸烟状态、种族、表现状态、TNM 分类和肺癌组织学类型时,AHRR(cg05575921)甲基化与生存无关。

结论

AHRR(cg05575921)甲基化与吸烟有关,但不能为肺癌患者提供独立的预后信息。

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