Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study.
Gut
; 64(3): 388-96, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25379950
ABSTRACT
BACKGROUND:
Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation.OBJECTIVE:
To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels.DESIGN:
Patients with early gastric cancer, aged 40-80â years, who planned to have, or had undergone, ER, were enrolled at least 6â months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1â year after the enrolment.RESULTS:
Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97â years. Authentic metachronous gastric cancers developed in 66 patients 29, 16 and 21 patients at 1-2, 2-3 and ≥3â years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1.CONCLUSIONS:
Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article