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Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single\u2010nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log\u2010additive model. Furthermore, several of these miRNAs passed the gene\u2010based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR\u201029a\/miR\u201029b\u20101 cluster were associated with diffuse subtype (minimum <jats:italic>p<\/jats:italic>\u2010value\u2009=\u20091.7 \u00d7 10<jats:sup>\u22124<\/jats:sup>; odds ratio, OR\u2009=\u20091.72; 95% confidence interval, CI\u2009=\u20091.30\u20132.28), two tagSNPs of the miR\u201025\/miR\u201093\/miR\u2010106b cluster were associated with cardia GC (minimum <jats:italic>p<\/jats:italic>\u2010value\u2009=\u20095.38 \u00d7 10<jats:sup>\u22123<\/jats:sup>; OR\u2009=\u20090.56, 95% CI\u2009=\u20090.37\u20130.86) and one tagSNP of the miR\u2010363\/miR\u201092a\u20102\/miR\u201019b\u20102\/miR\u201020b\/miR\u201018b\/miR\u2010106a cluster was associated with noncardia GC (minimum <jats:italic>p<\/jats:italic>\u2010value\u2009=\u20095.40 \u00d7 10<jats:sup>\u22123<\/jats:sup>; OR\u2009=\u20091.41, 95% CI\u2009=\u20091.12\u20131.78). Some functionally validated target genes of these miRNAs are implicated in cancer\u2010related processes such as methylation (<jats:italic>DNMT3A<\/jats:italic>, <jats:italic>DNMT3B<\/jats:italic>), cell cycle (<jats:italic>E2F1<\/jats:italic>, <jats:italic>CDKN1A<\/jats:italic>, <jats:italic>CDKN1C<\/jats:italic>), apoptosis (<jats:italic>BCL2L11<\/jats:italic>, <jats:italic>MCL1<\/jats:italic>), angiogenesis (<jats:italic>VEGFA<\/jats:italic>) and progression (<jats:italic>PIK3R1<\/jats:italic>, <jats:italic>MYCN<\/jats:italic>). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in <jats:italic>MIR29<\/jats:italic>, <jats:italic>MIR25<\/jats:italic>, <jats:italic>MIR93<\/jats:italic> and <jats:italic>MIR106b<\/jats:italic> may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.<\/jats:p>","DOI":"10.1002\/ijc.28850","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T11:06:54Z","timestamp":1395140814000},"page":"2065-2076","source":"Crossref","is-referenced-by-count":50,"title":["Genetic association of gastric cancer with miRNA clusters including the cancer\u2010related genes <i>MIR29, MIR25, MIR93<\/i> and <i>MIR106<\/i>: Results from the EPIC\u2010EURGAST study"],"prefix":"10.1002","volume":"135","author":[{"given":"Yolanda","family":"Espinosa\u2010Parrilla","sequence":"first","affiliation":[{"name":"Institut de Biologia Evolutiva, CSIC\u2010Universitat Pompeu Fabra Departament de Ci\u00e8ncies Experimentals i de la Salut, UPF, Barcelona Spain"},{"name":"Programa de Gen\u00e9tica Humana ICBM, Facultad de Medicina, Universidad de Chile, Santiago de Chile Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology Group Translational Research Laboratory, Catalan Institute of Oncology\u2010IDIBELL Barcelona Spain"},{"name":"Human Molecular Genetics Group Bellvitge Biomedical Research Institute (IDIBELL) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Bonet","sequence":"additional","affiliation":[{"name":"Unit of Nutrition Environment and Cancer Cancer Epidemiology Research 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