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

AbstractBladder 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 sign ificantly 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-rel ated CpGs alongside smoking metrics (AUC: 0.63–0.65). Further, PC1 re...
Source: European Journal of Epidemiology - Category: Epidemiology Source Type: research