title: LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.
abstract: Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fiano
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zugna
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Grasso
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Trevisan
authors.affiliation: b Division of Pathology, A.O. Città della Salute e della Scienza Hospital , Turin , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Delsedime
authors.affiliation: b Division of Pathology, A.O. Città della Salute e della Scienza Hospital , Turin , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Molinaro
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gillio-Tos
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.affiliation: a Cancer Epidemiology Unit-CERMS , Department of Medical Sciences , University of Turin and CPO-Piemonte , Turin , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019175:DNA Methylation; D056726:Genetic Association Studies; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
keywords: Global hypomethylation; LINE-1; methylation; mortality; non-neoplastic tissue; prostate cancer