ArticleProstate cancer and prostatic diseases2019
Single-nucleotide polymorphisms in DNMT3B gene and DNMT3B mRNA expression in association with prostate cancer mortality.
Article in Prostate cancer and prostatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 7 citations in OpenAlex.
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- A cellular senescence-related gene prognostic index for biochemical recurrence and drug resistance in patients with prostate cancer.American journal of cancer research · 2022Article
- Expression of epigenetic pathway related genes in association with PD-L1, ER/PgR and MLH1 in endometrial carcinoma.PloS one · 2022Article
- Regulation ofCancer management and research · 2020Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundGermline variants in DNA methyltransferase 3B (DNMT3B) may influence DNMT3B enzymatic activity, which, in turn, may affect cancer aggressiveness by altering DNA methylation.
methodsThe study involves two Italian cohorts (NTAT cohort, n = 157, and 1980s biopsy cohort, n = 182) and two U.S. cohorts (Health Professionals Follow-Up Study, n = 214, and Physicians' Health Study, n = 298) of prostate cancer (PCa) patients, and a case-control study of lethal (n = 113) vs indolent (n = 290) PCa with DNMT3B mRNA expression data nested in the U.S. cohorts. We evaluated the association between: three selected DNMT3B variants and global DNA methylation using linear regression in the NTAT cohort, the three DNMT3B variants and PCa mortality using Cox proportional hazards regression in all cohorts, and DNMT3B expression and lethal PCa using logistic regression, with replication in publicly available databases (TCGA, n = 492 and MSKCC, n = 140).
resultsThe TT genotype of rs1569686 was associated with LINE-1 hypomethylation in tumor tissue (β = -2.71, 95% CI: -5.41, -0.05). There was no evidence of association between DNMT3B variants and PCa mortality. DNMT3B expression was consistently associated with lethal PCa in the two U.S. cohorts (3rd vs 1st tertile, combined cohorts: OR = 2.04, 95% CI: 1.13, 3.76); the association was replicated in TCGA and MSKCC data (3rd vs 1st tertile, TCGA: HR = 3.00, 95% CI: 1.78, 5.06; MSKCC: HR = 2.22, 95% CI: 1.01, 4.86).
conclusionsAlthough there was no consistent evidence of an association between DNMT3B variants and PCa mortality, the TT genotype of rs1569686 was associated with LINE-1 hypomethylation in tumor tissue and DNMT3B mRNA expression was associated with an increased risk of lethal PCa.
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