Amaral, André F.S.Tajuddin, Salman MuhammadFernández, Agustín F.Chanock, Stephen J.Silverman, Debra T.Tardón, AdoninaCarrato, AlfredoGarcía Closas, MontserratJackson, Brian P.Toraño, EstelaMárquez, MiriamGonzález Urdinguio, RocíoGarcía Closas, ReinaRothman, NathanielKogevinas, ManolisReal, Francisco X.Fernández Fraga, MarioMalats i Riera, Núria2015-06-022015-06-022014Tajuddin SM, Amaral AF, Fernández AF, Chanock S, Silverman DT, Tardón A et al. LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk. British Journal of Cancer. 2014;(110):2123-30. DOI: 10.1038/bjc.2014.670007-0920http://hdl.handle.net/10230/23703Background: 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.application/pdfengThis work is published under the standard license to publish agreement./nAfter 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.LeucòcitsBufeta -- Càncerinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/bjc.2014.67Bladder cancerLINE-1 repetitive sequencesDNA methylationOne-carbon metabolismEpigenetic–gene interactioninfo:eu-repo/semantics/openAccess