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 language | English (US) |
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Pages (from-to) | 2123-2130 |
Number of pages | 8 |
Journal | British journal of cancer |
Volume | 110 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cancer Research