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Title: Smoking Methylation Marks for Prediction of Urothelial Cancer Risk.
Austin Authors: Yu, Chenglong;Jordahl, Kristina M;Bassett, Julie K;Joo, Jihoon Eric;Wong, Ee Ming;Brinkman, Maree T;Schmidt, Daniel F;Bolton, Damien M ;Makalic, Enes;Brasky, Theodore M;Shadyab, Aladdin H;Tinker, Lesley F;Longano, Anthony;Hopper, John L;English, Dallas R;Milne, Roger L;Bhatti, Parveen;Southey, Melissa C;Giles, Graham G;Dugué, Pierre-Antoine
Affiliation: Olivia Newton-John Cancer Wellness and Research Centre..
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia..
Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia..
Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia..
Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington..
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington..
Department of Anatomical Pathology, Eastern Health, Box Hill Hospital, Box Hill, Victoria, Australia..
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia..
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia..
Department of Data Science & AI, Faculty of IT, Monash University, Clayton, Victoria, Australia..
Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, Ohio..
Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California..
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington..
Cancer Control Research, BC Cancer Research Centre, Vancouver, British Columbia, Canada..
Issue Date: Dec-2021
Date: 2021-09-14
Publication information: Cancer epidemiology, biomarkers & prevention 2021; 30(12): 2197-2206
Abstract: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC). The meta-analysis identified associations (P < 4.7 × 10-5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P < 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set in MCCS [N = 134; odds ratio per SD (OR) = 1.37; 95% CI, 1.00-1.90] after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (N = 440; OR = 1.09; 95% CI, 0.91-1.30). Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger data sets. DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.
DOI: 10.1158/1055-9965.EPI-21-0313
ORCID: 0000-0001-5165-5769
Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
PubMed URL: 34526299
PubMed URL: 0000-0002-5145-6783
Type: Journal Article
Appears in Collections:Journal articles

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