title: Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the European Prospective Investigation into Nutrition and Cancer (EPIC-Italy) cohort.
abstract: The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset.
authors.affiliation: Department of Computer Science, University of Torino, Corso Svizzera 185, 10149 Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.affiliation: Department of Computer Science, University of Torino, Corso Svizzera 185, 10149 Turin, Italy, Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrero
authors.affiliation: Molecular and Genetic Epidemiology Unit and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.affiliation: Genomic Variation in Human Populations and Complex Diseases Unit, Human Genetics Foundation, Via Nizza 52, 10126 Turin, Italy, Department of Clinical and Biological Sciences, University of Torino, Via Santena 7, 10126 Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fiorito
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus Norfolk Place W2 1PG London, UK.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campanella
authors.affiliation: Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza-University of Torino and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Via delle Oblate 4, 50141 Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.affiliation: Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Frasca
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Via delle Oblate 4, 50141 Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Molecular and Genetic Epidemiology Unit and MRC-PHE Centre for Environment and Health, Imperial College London, St Mary's Campus Norfolk Place W2 1PG London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Molecular and Genetic Epidemiology Unit and alessio.naccarati@hugef-torino.org.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007558:Italy; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis
chemical_list: D035683:MicroRNAs