Methylation scores for smoking, alcohol consumption and body mass index and risk of seven types of cancer

Abstract

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven casecontrol studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1-1.2) for BMI and alcohol MS with several cancer types Abbreviations: AHRR, aryl hydrocarbon receptor repressor; AUC, area under the receiver operating characteristic curve; BMI, body mass index; EWAS, epigenome-wide association study;

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“…Pierre-Antoine Dugué 1,2,3 Chenglong Yu 1 Allison M. Hodge 2,3 Ee Ming Wong 1,4 JiHoon E. Joo 5 Chol-Hee Jung 6 Daniel Schmidt 3,7 Enes Makalic 3 Daniel D. Buchanan 5,6,8 Gianluca Severi 9 Dallas R. English 2,3 John L. Hopper 3 Roger L. Milne 1,2,3 Graham G. Giles 1,2,3 Melissa C. Southey 1,2,4 1…”