NDLI: DNA methyltransferase 3b (DNMT3b), tumor tissue DNA methylation, Gleason score, and prostate cancer mortality: investigating causal relationships

Content Provider	Springer Nature Link
Author	Gillio Tos, Anna Fia, Valentina Zugna, Daniela Vizzini, Loredana Pearce, Neil Delsedime, Luisa Merletti, Franco Richiardi, Lorenzo
Copyright Year	2012
Abstract	Aberrant DNA methylation plays a role in prostate cancer progression. We studied the relationships among DNA methyltransferase (DNMT) genotype, DNA methylation, Gleason score, and mortality in two cohorts of prostate cancer patients, previously reported with associations between DNA methylation in GSTP1, APC, and RUNX3 and prostate cancer mortality. Herein, we considered possible causal relationships between the studied variables, assuming that (1) DNMT activity affects tumor tissue methylation, (2) methylation status affects tumor morphology, and thus the Gleason score, and (3) DNA methylation affects mortality via Gleason score.The cohorts comprised 438 patients diagnosed at one Italian pathology ward before 1997, with DNA obtained from paraffin-embedded tumor tissues. The polymorphism rs406193 in the DNMT3b gene was assessed by allele discrimination in real-time PCR. According to the assumed causal model, we analyzed the effects of rs406193 (T carriers vs others) on the Gleason score without adjusting for gene methylation, and the effects of rs406193 on gene methylation and prostate cancer mortality without adjusting for Gleason score.We found no evidence of association between T carriers and the number of methylated genes. However, T carriers had reduced risk of a Gleason score 8+ (odds ratio = 0.57, 95 % CI 0.39–0.85), and a hazard ratio of 0.81 (0.61–1.09) of dying from prostate cancer, which would have been erroneously estimated of 0.93 if adjusted for Gleason score.These findings provide clues on the role of a DNMT3b SNP in prostate cancer progression and illustrate the importance of considering possible causal relationships in the analyses.
Starting Page	1549
Ending Page	1555
Page Count	7
File Format	PDF
ISSN	09575243
Journal	Cancer Causes & Control
Volume Number	23
Issue Number	9
e-ISSN	15737225
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-07-19
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	DNA methylation DNA methyltransferase 3b Prostate cancer Gleason score Mortality Causal relationship Public Health/Gesundheitswesen Cancer Research Biomedicine general Oncology Hematology Epidemiology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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