LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk

Amaral, André F.S.; Tajuddin, Salman Muhammad; Fernández, Agustín F.; Chanock, Stephen J.; Silverman, Debra T.; Tardón, Adonina; Carrato, Alfredo; García Closas, Montserrat; Jackson, Brian P.; Toraño, Estela; Márquez, Miriam; González Urdinguio, Rocío; García Closas, Reina; Rothman, Nathaniel; Kogevinas, Manolis; Real, Francisco X.; Fernández Fraga, Mario; Malats i Riera, Núria

LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk

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dc.contributor.author Amaral, André F.S.ca
dc.contributor.author Tajuddin, Salman Muhammadca
dc.contributor.author Fernández, Agustín F.ca
dc.contributor.author Chanock, Stephen J.ca
dc.contributor.author Silverman, Debra T.ca
dc.contributor.author Tardón, Adoninaca
dc.contributor.author Carrato, Alfredoca
dc.contributor.author García Closas, Montserratca
dc.contributor.author Jackson, Brian P.ca
dc.contributor.author Toraño, Estelaca
dc.contributor.author Márquez, Miriamca
dc.contributor.author González Urdinguio, Rocíoca
dc.contributor.author García Closas, Reinaca
dc.contributor.author Rothman, Nathanielca
dc.contributor.author Kogevinas, Manolisca
dc.contributor.author Real, Francisco X.ca
dc.contributor.author Fernández Fraga, Marioca
dc.contributor.author Malats i Riera, Núriaca
dc.date.accessioned 2015-06-02T08:10:47Z
dc.date.available 2015-06-02T08:10:47Z
dc.date.issued 2014ca
dc.description.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.en
dc.description.sponsorship This work was supported by the Association for International Cancer Research (grant number 09-0780); Fondo de Investigación Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Temática de Investigación Cooperativa en Cáncer (grant number RD12/0036/0050-RTICC), Spain; European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; EU-FP7-HEALTH-F2-2008-201333-DECanBio); Fundación Científica de la AECC, Spain; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USAen
dc.format.mimetype application/pdfca
dc.identifier.citation Tajuddin 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.2014.67ca
dc.identifier.doi http://dx.doi.org/10.1038/bjc.2014.67
dc.identifier.issn 0007-0920ca
dc.identifier.uri http://hdl.handle.net/10230/23703
dc.language.iso engca
dc.publisher Cancer Research UKca
dc.relation.ispartof British Journal of Cancer. 2014;(110):2123-30
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201663
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201333
dc.rights This 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.en
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subject.keyword Bladder canceren
dc.subject.keyword LINE-1 repetitive sequencesen
dc.subject.keyword DNA methylationen
dc.subject.keyword One-carbon metabolismen
dc.subject.keyword Epigenetic–gene interactionen
dc.subject.other Leucòcitsca
dc.subject.other Bufeta -- Càncerca
dc.title LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risken
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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