Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.

IF 5.7 2区医学 Q1 Medicine

Cancer Science Pub Date : 2024-12-03 DOI:10.1111/cas.16414

Zitong Zhao, Megha Bhardwaj, Ziwen Fan, Xianzhe Li, Petra Schrotz-King, Hermann Brenner

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引用次数: 0

Abstract

Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (n = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63-0.78]), while cg11385536 (1.04 [1.01-1.07]), cg09736286 (1.64 [1.10-2.44]), cg19907023 (1.64 [1.01-2.66]), and cg22032485 (1.52 [1.04-2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.

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来源期刊

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.