Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma.
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.
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Shu-Mei
SM
Yang
Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
Chao-Yuan
CY
Huang
Department of Chinese Medicine, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Horng-Sheng
HS
Shiue
Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
Yeong-Shiau
YS
Pu
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Yi-Hsun
YH
Hsieh
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Wei-Jen
WJ
Chen
Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
Ying-Chin
YC
Lin
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ymhsueh@tmu.edu.tw.
Yu-Mei
YM
Hsueh
D001151:Arsenic / Q000652:urine*; D002273:Carcinogens / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004785:Environmental Pollutants / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D002273:Carcinogens; C000717967:DNMT3A protein, human; D004785:Environmental Pollutants; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619380:DNMT1 protein, human; D001151:Arsenic
Arsenic; DNMT; Renal cell carcinoma