Dataset Information

LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

ABSTRACT: DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with ? regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 ?g/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted.

SUBMITTER: Salas LA

PROVIDER: S-EPMC4622716 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

Salas Lucas A LA Villanueva Cristina M CM Tajuddin Salman M SM Amaral André F S AF Fernandez Agustín F AF Moore Lee E LE Carrato Alfredo A Tardón Adonina A Serra Consol C García-Closas Reina R Basagaña Xavier X Rothman Nathaniel N Silverman Debra T DT Cantor Kenneth P KP Kogevinas Manolis M Real Francisco X FX Fraga Mario F MF Malats Núria N

Epigenetics 20141101 11

DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC condu ...[more]

PMID: 25482586

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Project description:DNA methylation profiles are responsive to environmental stimuli and metabolic shifts. This makes DNA methylation a potential biomarker of environmental-related and lifestyle-driven diseases of adulthood. Therefore, we investigated if white blood cells' (WBCs) DNA methylation profiles are associated with myocardial infarction (MI) occurrence. Whole-genome DNA methylation was investigated by microarray analysis in 292 MI cases and 292 matched controls from the large prospective Italian European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (EPICOR study). Significant signals (false discovery rate (FDR) adjusted P?<?0.05) were replicated by mass spectrometry in 317 MI cases and 262 controls from the Dutch EPIC cohort (EPIC-NL). Long interspersed nuclear element-1 (LINE-1) methylation profiles were also evaluated in both groups.A differentially methylated region (DMR) within the zinc finger and BTB domain-containing protein 12 (ZBTB12) gene body and LINE-1 hypomethylation were identified in EPICOR MI cases and replicated in the EPIC-NL sample (ZBTB12-DMR meta-analysis: effect size?±?se?=?-0.016?±?0.003, 95 % CI?=?-0.021;-0.011, P?=?7.54?×?10(-10); LINE-1 methylation meta-analysis: effect size?±?se?=?-0.161?±?0.040, 95 % CI?=?-0.239;-0.082, P?=?6.01?×?10(-5)). Moreover, cases with shorter time to disease had more pronounced ZBTB12-DMR hypomethylation (meta-analysis, men: effect size?±?se?=?-0.0059?±?0.0017, P TREND?=?5.0?×?10(-4); women: effect size?±?se?=?-0.0053?±?0.0019, P TREND?=?6.5?×?10(-3)) and LINE-1 hypomethylation (meta-analysis, men: effect size?±?se?=?-0.0010?±?0.0003, P TREND?=?1.6?×?10(-3); women: effect size?±?se?=?-0.0008?±?0.0004, P TREND?=?0.026) than MI cases with longer time to disease. In the EPIC-NL replication panel, DNA methylation profiles improved case-control discrimination and reclassification when compared with traditional MI risk factors only (net reclassification improvement (95 % CI) between 0.23 (0.02-0.43), P?=?0.034, and 0.89 (0.64-1.14), P?<?1?×?10(-5)).Our data suggest that specific methylation profiles can be detected in WBCs, in a preclinical condition, several years before the occurrence of MI, providing an independent signature of cardiovascular risk. We showed that prediction accuracy can be improved when DNA methylation is taken into account together with traditional MI risk factors, although further confirmation on a larger sample is warranted. Our findings support the potential use of DNA methylation patterns in peripheral blood white cells as promising early biomarkers of MI.

Dataset Information

LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

Publications

LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

Similar Datasets

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