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Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients.
Richiardi, Lorenzo; Fiano, Valentina; Vizzini, Loredana; De Marco, Laura; Delsedime, Luisa; Akre, Olof; Tos, Anna Gillio; Merletti, Franco.
Afiliación
  • Richiardi L; Cancer Epidemiology Unit, University of Turin, Via Santena 7, 10126 Turin, Italy. lorenzo.richiardi@unito.it
J Clin Oncol ; 27(19): 3161-8, 2009 Jul 01.
Article en En | MEDLINE | ID: mdl-19470943
PURPOSE There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. METHODS We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer-specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. CONCLUSION The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Genes APC / Metilación de ADN / Gutatión-S-Transferasa pi / Subunidad alfa 3 del Factor de Unión al Sitio Principal Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Humans / Male Idioma: En Revista: J Clin Oncol Año: 2009 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Genes APC / Metilación de ADN / Gutatión-S-Transferasa pi / Subunidad alfa 3 del Factor de Unión al Sitio Principal Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Humans / Male Idioma: En Revista: J Clin Oncol Año: 2009 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos