LINE-1 methylation in leukocyte DNA,interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk |
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Authors: | S M Tajuddin A F S Amaral A F Fernández S Chanock D T Silverman A Tardón A Carrato M García-Closas B P Jackson E G Tora?o M Márquez R G Urdinguio R García-Closas N Rothman M Kogevinas F X Real M F Fraga N Malats for the Spanish Bladder Cancer/EPICURO Study investigators |
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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. |
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Keywords: | bladder cancer, LINE-1 repetitive sequences, DNA methylation, one-carbon metabolism, epigenetic– gene interaction |
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