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Title: LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.
Authors: Tajuddin SM,  Amaral AF,  Fernández AF,  Chanock S,  Silverman DT,  Tardón A,  Carrato A,  García-Closas M,  Jackson BP,  Toraño EG,  Márquez M,  Urdinguio RG,  García-Closas R,  Rothman N,  Kogevinas M,  Real FX,  Fraga MF,  Malats N,  Spanish Bladder Cancer/EPICURO Study investigators,  Kogevinas M,  Malats N,  Real FX,  Sala M,  Castaño G,  Torà M,  Puente D,  Villanueva C,  Murta-Nascimento C,  Fortuny J,  López E,  Hernández S,  Jaramillo R,  Vellalta G,  Palencia L,  Fermández F,  Amorós A,  Alfaro A,  Carretero G,  Lloreta J,  Serrano S,  Ferrer L,  Gelabert A,  Carles J,  Bielsa O,  Villadiego K,  Cecchini L,  Saladié JM,  Ibarz L,  Céspedes M,  Serra C,  García D,  Pujadas J,  Hernando R,  Cabezuelo A,  Abad C,  Prera A,  Prat J,  Domènech M,  Badal J,  Malet J,  García-Closas R,  Rodríguez de Vera J,  Martín AI,  Taño J,  Cáceres F,  Carrato A,  García-López F,  Ull M,  Teruel A,  Andrada E,  Bustos A,  Castillejo A,  Soto JL,  Tardón A,  Guate JL,  Lanzas JM,  Velasco J,  Fernández JM,  Rodríguez JJ,  Herrero A,  Abascal R,  Manzano C,  Miralles T,  Rivas M,  Arguelles M,  Díaz M,  Sánchez J,  González O,  Mateos A,  Frade V,  Muntañola P,  Pravia C,  Huescar AM,  Huergo F,  Mosquera J
Journal: Br J Cancer
Date: 2014 Apr 15
Branches: LTG, OD, OEEB
PubMed ID: 24595004
PMC ID: PMC3992509
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.