A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer

IF 7.7 1区医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH European Journal of Epidemiology Pub Date : 2024-03-30 DOI:10.1007/s10654-024-01110-y

{"title":"A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer","authors":"","doi":"10.1007/s10654-024-01110-y","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case–control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine–phosphate–guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59–0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63–0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"75 1","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Epidemiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10654-024-01110-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}

引用次数: 0

Abstract

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case–control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine–phosphate–guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59–0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63–0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

与吸烟有关的白细胞 DNA 甲基化标记与膀胱癌风险的前瞻性研究

摘要膀胱癌是一种常见肿瘤，主要由吸烟引起。包括 DNA 甲基化在内的表观遗传学改变有可能被用作风险增加的前瞻性标记，尤其是在吸烟者等高危人群中。我们的目的是在前瞻性前列腺癌、肺癌、结肠直肠癌和卵巢癌（PLCO）筛查试验和α-生育酚、β-胡萝卜素癌症（ATBC）预防研究（789 例病例；849 例对照）的巢式病例对照研究中，研究与吸烟相关的白细胞（WBC）甲基化标记物对膀胱癌风险预测的潜在贡献，而非传统的基于问卷的吸烟指标（即持续时间、强度、包年）。在先前报告的 2670 个与吸烟相关的胞嘧啶-磷酸鸟嘌呤位点（CpGs）中，我们发现了 200 个与吸烟状态相关的不同甲基化位点，以及 28 个与膀胱癌风险显著相关的位点（经多重检验校正后）。在不同队列中也观察到了类似的模式。接收者操作特征（ROC）分析表明，cg05575921 (AHHR)是我们发现的膀胱癌风险中与吸烟相关性最强的基因，与经典的吸烟指标（AUC：0.59-0.62）相比，单独使用cg05575921 (AHHR)具有相似的预测性能（AUC：0.60）。将 200 个与吸烟相关的 CpGs 的第一个主成分（PC1）与吸烟指标一起纳入，可获得最佳预测效果（AUC：0.63-0.65）。此外，在对吸烟指标进行调整后，PC1 仍然与膀胱癌风险升高密切相关。这些研究结果表明，DNA甲基化图谱除了反映吸烟时间、强度和包年所捕获的信息外，还反映了烟草烟雾暴露的其他方面，以及/或与膀胱癌病因相关的个体易感性，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

European Journal of Epidemiology 医学-公共卫生、环境卫生与职业卫生

CiteScore

21.40

自引率

1.50%

发文量

109

审稿时长

6-12 weeks

期刊介绍： The European Journal of Epidemiology, established in 1985, is a peer-reviewed publication that provides a platform for discussions on epidemiology in its broadest sense. It covers various aspects of epidemiologic research and statistical methods. The journal facilitates communication between researchers, educators, and practitioners in epidemiology, including those in clinical and community medicine. Contributions from diverse fields such as public health, preventive medicine, clinical medicine, health economics, and computational biology and data science, in relation to health and disease, are encouraged. While accepting submissions from all over the world, the journal particularly emphasizes European topics relevant to epidemiology. The published articles consist of empirical research findings, developments in methodology, and opinion pieces.