Evidence for PTGER 4 , PSCA , and MBOAT 7 as risk genes for gastric cancer on the genome and transcriptome level

作者：Sophie K. M. Heinrichs, Timo Hess, Jessica Becker, Lutz Hamann, Yogesh K. Vashist, Katja Butterbach, Thomas Schmidt, Hakan Alakus, Iurii Krasniuk, A Höblinger, Philipp Lingohr, Monika Ludwig, Alexander Hagel, Claus Schildberg, Lothar Veits, Ugnė Gyvytė, Katharina Weise, Vitalia Schüller, Anne C. Böhmer, Julia Schröder, Jan Gehlen, Nicole Kreuser, Sebastian J. Hofer, Hauke Lang, Florian Lordick, Peter Malfertheiner, Markus Moehler, Oliver Pech, Nikolaos Vassos, Ernst Rodermann, Jakob R. Izbicki, M. Kruschewski, Katja Ott, Ralf R. Schumann, Michael Vieth, Elisabeth Mangold, Evita Gašenko, Limas Kupčinskas, Hermann Brenner, Peter Grimminger, Luís Bujanda, Federico Sopeña, Jesús Espinel, Concha Thomson, Ángeles Pérez‐Aísa, Rafael Campo, Fernando Geijo, Daniela Collette, Christiane J. Bruns, Katharina Messerle, Ines Gockel, Markus M. Nöthen, H. Lippert, Karsten Ridwelski, Ángel Lanas, Gisela Keller, Michael Knapp, Mārcis Leja, Juozas Kupčinskas, María Asunción García-González, Marino Venerito, Johannes Schumacher · 发表于：Cancer Medicine · 年份：2018 · DOI：10.1002/cam4.1719 · 被引用次数：28 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Abstract Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer ( GC ) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine‐mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus ( eQTL ) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 ( P = 2.53 × 10 −04 ) and on chromosome 8q24 at rs2585176 ( P = 1.09 × 10 −09 ). On chromosome 5p13 we found cis‐ eQTL effects with an upregulation of PTGER 4 expression in GC risk allele carrier ( P = 9.27 × 10 −11 ). On chromosome 8q24 we observed cis‐ eQTL effects with an upregulation of PSCA expression in GC risk allele carrier ( P = 2.17 × 10 −47 ). In addition, we found trans‐ eQTL effects for the same variants on 8q24 with a downregulation of MBOAT 7 expression in GC risk allele carrier ( P = 3.11 × 10 −09 ). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER 4 and PSCA as well as a downregulated expression of MBOAT 7 i...