skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

Abstract

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 withmore » concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.« less

Authors:
 [1];  [2];  [3];  [2]; ;  [1];  [4];  [1]
  1. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)
  2. Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China)
  3. Department of Chinese Medicine, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (China)
  4. Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan (China)
Publication Date:
OSTI Identifier:
22689228
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 305; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABSORPTION; ABSORPTION SPECTROSCOPY; ARSENIC; CARCINOMAS; CHAIN REACTIONS; DNA; ENZYME ACTIVITY; GENOTYPE; HAZARDS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; HOSPITALS; KIDNEYS; METHYL TRANSFERASES; NUCLEOTIDES; POLYMERASE CHAIN REACTION; POLYMERASES

Citation Formats

Yang, Shu-Mei, Huang, Chao-Yuan, Shiue, Horng-Sheng, Pu, Yeong-Shiau, Hsieh, Yi-Hsun, Chen, Wei-Jen, Lin, Ying-Chin, Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, Hsueh, Yu-Mei, and Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma. United States: N. p., 2016. Web. doi:10.1016/J.TAAP.2016.06.011.
Yang, Shu-Mei, Huang, Chao-Yuan, Shiue, Horng-Sheng, Pu, Yeong-Shiau, Hsieh, Yi-Hsun, Chen, Wei-Jen, Lin, Ying-Chin, Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, Hsueh, Yu-Mei, & Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma. United States. https://doi.org/10.1016/J.TAAP.2016.06.011
Yang, Shu-Mei, Huang, Chao-Yuan, Shiue, Horng-Sheng, Pu, Yeong-Shiau, Hsieh, Yi-Hsun, Chen, Wei-Jen, Lin, Ying-Chin, Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, Hsueh, Yu-Mei, and Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 2016. "Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma". United States. https://doi.org/10.1016/J.TAAP.2016.06.011.
@article{osti_22689228,
title = {Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma},
author = {Yang, Shu-Mei and Huang, Chao-Yuan and Shiue, Horng-Sheng and Pu, Yeong-Shiau and Hsieh, Yi-Hsun and Chen, Wei-Jen and Lin, Ying-Chin and Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan and Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan and Hsueh, Yu-Mei and Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan},
abstractNote = {Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.},
doi = {10.1016/J.TAAP.2016.06.011},
url = {https://www.osti.gov/biblio/22689228}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 305,
place = {United States},
year = {Mon Aug 15 00:00:00 EDT 2016},
month = {Mon Aug 15 00:00:00 EDT 2016}
}