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ABSTRACT: Background
Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors.Methods
Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed.Results
The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05).Conclusions
The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.
SUBMITTER: Tajuddin SM
PROVIDER: S-EPMC3992509 | biostudies-literature | 2014 Apr
REPOSITORIES: biostudies-literature
Tajuddin S M SM Amaral A F S AF Fernández A F AF Chanock S S Silverman D T DT Tardón A A Carrato A A García-Closas M M Jackson B P BP Toraño E G EG Márquez M M Urdinguio R G RG García-Closas R R Rothman N N Kogevinas M M Real F X FX Fraga M F MF Malats N N
British journal of cancer 20140304 8
<h4>Background</h4>Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors.<h4>Methods</h4>Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyroseque ...[more]