title: Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma.
abstract: Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case-control study between June 2011 and August 2014. We collected environmental exposure-related information with questionnaires. Blood and urine samples were analyzed to measure the Cd and Pb exposure and 5-methyl-2'-deoxycytidine levels as a proxy for DNA methylation. Multivariate logistic regression and 95% confidence intervals were applied to estimate the risk for UC. Study participants with high Cd and Pb exposure in blood or urine had significantly increased risk of UC, especially among the smokers. After adjusting for age and gender, the possible connections of individual cumulative cigarette smoking or herb medicine exposure with the increased levels of Cd and Pb were observed in the controls. Participants with 8.66%-12.39% of DNA hypomethylation had significantly increased risk of UC compared with those with ≥12.39% of DNA hypomethylation. Environmental factors including cigarette smoking and herb medicine may contribute to the internal dose of heavy metals levels. Repeat measurements of heavy metals with different study design, detailed dietary information, and types of herb medicine should be recommended for exploring UC carcinogenesis in future studies.
authors.affiliation: Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Chung
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung, Taiwan; Department of Medicine, College of Medicine, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Chao-Hsiang
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Saou-Hsing
authors.initials: SH
authors.lastname: Liou
authors.affiliation: Department of Family Medicine, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Chiu-Shong
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jhih-Sheng
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 076308@mail.fju.edu.tw.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002104:Cadmium / Q000378:metabolism* / Q000633:toxicity; D016022:Case-Control Studies; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D007854:Lead / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism*; D014571:Urologic Neoplasms / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D002104:Cadmium; D007854:Lead
keywords: Cigarette smoking; Global DNA methylation; Heavy metals; Herbal medicine; Urothelial carcinoma