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Maternal smoking induces widespread and long-lasting DNA methylation changes, which we study here for association with risk of cancer in adulthood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight prospective case\u2013control studies nested within the Melbourne Collaborative Cohort Study were used to assess associations between maternal-smoking-associated methylation marks in blood and risk of several cancers: breast (n\u2009=\u2009406 cases), colorectal (n\u2009=\u2009814), gastric (n\u2009=\u2009166), kidney (n\u2009=\u2009139), lung (n\u2009=\u2009327), prostate (n\u2009=\u2009847) and urothelial (n\u2009=\u2009404) cancer and B-cell lymphoma (n\u2009=\u2009426). We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between cancer and five methylation scores calculated as weighted averages for 568, 19, 15, 28 and 17 CpG sites. Models were adjusted for confounders, including personal smoking history (smoking status, pack-years, age at starting and quitting) and methylation scores for personal smoking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All methylation scores for maternal smoking were strongly positively associated with risk of urothelial cancer. Risk estimates were only slightly attenuated after adjustment for smoking history, other potential confounders and methylation scores for personal smoking. Potential negative associations were observed with risk of lung cancer and B-cell lymphoma. No associations were observed for other cancers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We found that methylation marks of prenatal exposure to maternal smoking are associated with increased risk of urothelial cancer. Our study demonstrates the potential for using DNA methylation to investigate the impact of early-life, unmeasured exposures on later-life cancer risk.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ije\/dyaa210","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T03:38:29Z","timestamp":1601350709000},"page":"105-115","source":"Crossref","is-referenced-by-count":24,"title":["Methylation marks of prenatal exposure to maternal smoking and risk of cancer in adulthood"],"prefix":"10.1093","volume":"50","author":[{"given":"Pierre-Antoine","family":"Dugu\u00e9","sequence":"first","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia"},{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 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