Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients.
Carcinogenesis
; 38(8): 821-826, 2017 08 01.
Article
em En
| MEDLINE
| ID: mdl-28854562
ABSTRACT
Global DNA methylation may affect chromosome structure and genomic stability and is involved in carcinogenesis. In this study, we aimed to investigate whether methylation of pericentromeric repeat NBL2 and subtelomeric repeat D4Z4 in peripheral blood was associated with the aggressiveness of prostate cancer (PCa). We measured the methylation status of different CpG sites of NBL2 and D4Z4 in 795 PCa patients and compared their methylation levels among patients with different Gleason Score at diagnosis. We then analyzed the association of the NBL2 and D4Z4 methylation with the risk of biochemical recurrence (BCR) in patients receiving radical prostatectomy or radiotherapy using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation. There was no significant difference in methylation level of NBL2 and D4Z4 between clinically defined aggressive and non-aggressive PCa at diagnosis. However, the methylation of D4Z4 was associated with BCR, while the methylation of NBL2 was not. In tertile analysis, patients in the highest tertile of D4Z4 methylation had an increased risk of BCR (HR = 2.17, 95% CI 1.36-3.48) compared to patients in the lower tertiles after adjustment of age, body mass index, smoking status, pack year, D'Amico risk groups and treatments. Among the four CpG sites in this region, the association was mostly attributable to the methylation of the second CpG site of D4Z4. These data suggest that higher methylation in D4Z4 was associated with worse prognosis of localized PCa patients.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Biomarcadores Tumorais
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Metilação de DNA
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Recidiva Local de Neoplasia
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos