title: Mediterranean diet-gene interactions: A targeted metabolomics study in Greek-Cypriot women.
abstract: A high adherence to the Mediterranean diet (MD) was previously associated with a decreased risk of breast cancer (BC) among Greek-Cypriot women. Additionally, particular polymorphisms were shown to modulate this MD-BC association. Herein, we aimed to investigate the effect of polymorphisms-MD interactions on the levels of specific metabolites that could be related to dietary adherence or enzymatic activity, which is itself modulated by polymorphisms.
  
  
  
  Greek-Cypriot women who were BC controls and had the lowest or the highest MD adherence (vegetables, fruit, legumes, fish) as assessed by principal component analysis (n = 564) were included. Participants were previously genotyped for nine polymorphisms of the one-carbon metabolism, oxidative stress, and xenobiotic metabolism. The serum levels of 14 metabolites that are key players in the aforementioned pathways were measured by UPLC-MS/MS. ANCOVA was used to assess polymorphism-MD interactions on metabolites' levels within a multivariate linear regression model. Statistically significant interactions between GSTM1 (where GST is glutathione S-transferase) deletion polymorphism and MD on flavin mononucleotide and on 5-methyltetrahydrofolate (5-MTHF) concentrations were observed. The MTHFR rs1801133 interacted significantly with MD on 5-MTHF concentration.
  
  
  
  Serum levels of flavin mononucleotide and 5-MTHF were shown to be influenced by interactions between GSTM1 deletion or MTHFR (rs1801133) polymorphisms and a dietary pattern, characteristic of MD.
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.|The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kakkoura
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Kleitos
authors.initials: K
authors.lastname: Sokratous
authors.affiliation: The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.|Neurology Clinic D, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Christiana A
authors.initials: CA
authors.lastname: Demetriou
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Loizidou
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Loucaides
authors.affiliation: Department of Medical Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kakouri
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.|The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.|The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000178:diet therapy*; D038441:Diet, Mediterranean; D007887:Fabaceae; D005260:Female; D005638:Fruit; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006115:Greece; D006801:Humans; D055432:Metabolomics; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D013763:Tetrahydrofolates; D014675:Vegetables
chemical_list: D013763:Tetrahydrofolates; D005982:Glutathione Transferase; C005984:5-methyltetrahydrofolate
keywords: Mediterranean dietary pattern; Nutrigenetics; One-carbon metabolism; Serum-targeted metabolomics; Xenobiotic metabolism