DNA methylation, colon cancer and Mediterranean diet: results from the EPIC-Italy cohort.
Epigenetics
; 14(10): 977-988, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31179817
ABSTRACT
The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a 'meet-in-the-middle' approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias del Colon
/
Metilación de ADN
/
Subunidad alfa 1 del Factor de Unión al Sitio Principal
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Epigenetics
Asunto de la revista:
GENETICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia