Dataset Information

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

ABSTRACT: 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.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.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).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.

SUBMITTER: Tajuddin SM

PROVIDER: S-EPMC3992509 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Tajuddin S M SM Amaral A F S AF Fernández A F AF Chanock S S Silverman D T DT Tardón A A Carrato A A García-Closas M M Jackson B P BP Toraño E G EG Márquez M M Urdinguio R G RG García-Closas R R Rothman N N Kogevinas M M Real F X FX Fraga M F MF Malats N N

British journal of cancer 20140304 8

<h4>Background</h4>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.<h4>Methods</h4>Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyroseque ...[more]

PMID: 24595004

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Project description:BackgroundChanges in DNA methylation over the course of life may provide an indicator of risk for cancer. We explored longitudinal changes in CpG methylation from blood leukocytes, and likelihood of future cancer diagnosis.MethodsPeripheral blood samples were obtained at baseline and at follow-up visit from 20 participants in the Health, Aging and Body Composition prospective cohort study. Genome-wide CpG methylation was assayed using the Illumina Infinium Human MethylationEPIC (HM850K) microarray.ResultsGlobal patterns in DNA methylation from CpG-based analyses showed extensive changes in cell composition over time in participants who developed cancer. By visit year 6, the proportion of CD8+ T-cells decreased (p-value = 0.02), while granulocytes cell levels increased (p-value = 0.04) among participants diagnosed with cancer compared to those who remained cancer-free (cancer-free vs. cancer-present: 0.03 ± 0.02 vs. 0.003 ± 0.005 for CD8+ T-cells; 0.52 ± 0.14 vs. 0.66 ± 0.09 for granulocytes). Epigenome-wide analysis identified three CpGs with suggestive p-values ≤10- 5 for differential methylation between cancer-free and cancer-present groups, including a CpG located in MTA3, a gene linked with metastasis. At a lenient statistical threshold (p-value ≤3 × 10- 5), the top 10 cancer-associated CpGs included a site near RPTOR that is involved in the mTOR pathway, and the candidate tumor suppressor genes REC8, KCNQ1, and ZSWIM5. However, only the CpG in RPTOR (cg08129331) was replicated in an independent data set. Analysis of within-individual change from baseline to Year 6 found significant correlations between the rates of change in methylation in RPTOR, REC8 and ZSWIM5, and time to cancer diagnosis.ConclusionThe results show that changes in cellular composition explains much of the cross-sectional and longitudinal variation in CpG methylation. Additionally, differential methylation and longitudinal dynamics at specific CpGs could provide powerful indicators of cancer development and/or progression. In particular, we highlight CpG methylation in the RPTOR gene as a potential biomarker of cancer that awaits further validation.

Dataset Information

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

Publications

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

Similar Datasets

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