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

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. Toraño, M. Márquez, R. G. Urdinguio, R. García-Closas, N. Rothman, M. Kogevinas, F. X. Real, M. F. Fraga, N. Malats

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2123-2130
Number of pages8
JournalBritish journal of cancer
Volume110
Issue number8
DOIs
StatePublished - Apr 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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