Association of somatic DNA methylation variability with progression-free survival and toxicity in ovarian cancer patients.
Ann Oncol
; 24(11): 2813-8, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24114859
BACKGROUND: We have addressed whether inter-individual methylation variation in somatic (white blood cells, WBCs) DNA of ovarian cancer patients provides potential for prognostic and/or pharmacoepigenetic stratification. PATIENTS AND METHODS: WBC DNA methylation was analysed by bisulphite pyrosequencing at ataxia telangiectasia mutated (ATM), estrogen receptor 1 (ESR1), progesterone receptor (PGR), mutL homologue 1 (MLH1), breast cancer susceptibility gene (BRCA1), secreted frizzled-related protein 1 (SFRP1), stratifin (SFN), retinoic acid receptor beta (RARB) loci and the repetitive element LINE1 in 880 SCOTROC1 trial patients [paclitaxel (Taxol)-carboplatin versus docetaxel (Taxotere)-carboplatin as primary chemotherapy for stage Ic-IV epithelial ovarian cancer]. RESULTS: We observed no significant associations (P < 0.005, after correction for multiple testing) for progression-free survival (PFS) using test and validation sets. However, we did identify mean SFN methylation associated with PFS (hazard ratio, HR = 1.01 per 1% increase in methylation, q = 0.028); particularly in the paclitaxel (HR = 1.01, q = 0.006), but not in the docetaxel arm in stratified analyses. Furthermore, higher methylation within the ESR1 gene was associated with CA125 response (odds ratio, OR = 1.06, q = 0.04) and with neuropathy (HR = 0.95, q = 0.002), but only in the paclitaxel arm of the trial. CONCLUSIONS: This is the first study linking DNA methylation variability in WBC to clinical outcomes for any tumour type; the data generated on novel prognostic and pharmacoepigenetic DNA methylation biomarkers in the circulation now need independent further evaluation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Biomarcadores Tumorais
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Metilação de DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article