title: Methylation patterns in sentinel genes in peripheral blood cells of heavy smokers: Influence of cruciferous vegetables in an intervention study.
abstract: Changes in DNA methylation patterns are a hallmark of tobacco-induced carcinogenesis. We have conducted a randomized 4-week intervention trial to investigate the effects of three dietary regimens to modify DNA methylation patterns in peripheral white blood cells of heavy smokers. A group of 88 smokers were randomly assigned to and distributed among three diets, including (1) normal isocaloric diet (balanced in fruits and vegetables), according to international guidelines; (2) a diet enriched in flavonoids and isothiocyanates (particularly cruciferous vegetables); (3) a regimen consisting of diet 1 supplemented with flavonoids (green tea and soy products). Methylation patterns were analyzed by pyrosequencing in LINE1 (Long Interspersed DNA Elements), RASSF1A, ARF and CDKN2a (tumor suppressor genes), MLH1 (mismatch DNA repair) and MTHFR (folate metabolism). Three distinct patterns of methylation were observed. In LINE1, methylation showed a small but reproducible increase with all three regimens. MTHFR was constitutively methylated with no significant modulation by diets. The four other loci showed low basal levels of methylation with no substantial change after intervention. These data suggest that the isocaloric diet may stabilize global epigenetic (LINE1 DNA methylation) patterns in peripheral white blood cells but does not provide evidence for methylation changes in specific genes associated with this short-term dietary intervention.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Scoccianti
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ricceri
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Cyrille
authors.initials: C
authors.lastname: Cuenin
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics; D019607:Brassicaceae / Q000737:chemistry*; D019175:DNA Methylation; D004032:Diet; D044127:Epigenesis, Genetic; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D019942:Genes, p16 / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology; D007962:Leukocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000737:chemistry / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D012907:Smoking / Q000097:blood* / Q000235:genetics; D013025:Glycine max / Q000737:chemistry; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005419:Flavonoids; D017879:Isothiocyanates; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000070957:MutL Protein Homolog 1