Heinrichs, Sophie K. M., Hess, Timo, Becker, Jessica, Hamann, Lutz, Vashist, Yogesh K., Butterbach, Katja, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Alakus, Hakan, Krasniuk, Iurii, Hoeblinger, Aksana, Lingohr, Philipp, Ludwig, Monika, Hagel, Alexander F., Schildberg, Claus W., Veits, Lothar, Gyvyte, Ugne ORCID: 0000-0002-1130-2472, Weise, Katharina, Schueller, Vitalia, Boehmer, Anne C., Schroeder, Julia, Gehlen, Jan, Kreuser, Nicole, Hofer, Sebastian, Lang, Hauke, Lordick, Florian, Malfertheiner, Peter, Moehler, Markus, Pech, Oliver, Vassos, Nikolaos, Rodermann, Ernst, Izbicki, Jakob R., Kruschewski, Martin, Ott, Katja, Schumann, Ralf R., Vieth, Michael, Mangold, Elisabeth, Gasenko, Evita, Kupcinskas, Limas, Brenner, Hermann, Grimminger, Peter, Bujanda, Luis, Sopena, Federico, Espinel, Jesus, Thomson, Concha, Perez-Aisa, Angeles, Campo, Rafael, Geijo, Fernando, Collette, Daniela, Bruns, Christiane, Messerle, Katharina, Gockel, Ines, Noethen, Markus M., Lippert, Hans, Ridwelski, Karsten, Lanas, Angel, Keller, Gisela, Knapp, Michael, Leja, Marcis, Kupcinskas, Juozas, Garcia-Gonzalez, Maria A., Venerito, Marino ORCID: 0000-0001-8581-0974 and Schumacher, Johannes (2018). Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level. Cancer Med., 7 (10). S. 5057 - 5066. HOBOKEN: WILEY. ISSN 2045-7634

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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 x 10(-04)) and on chromosome 8q24 at rs2585176 (P = 1.09 x 10(-09)). On chromosome 5p13 we found cis-eQTL effects with an up-regulation of PTGER4 expression in GC risk allele carrier (P = 9.27 x 10(-11)). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 x 10(-47)). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 x 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 PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Heinrichs, Sophie K. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vashist, Yogesh K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Butterbach, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, ThomasUNSPECIFIEDorcid.org/0000-0002-7166-3675UNSPECIFIED
Alakus, HakanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krasniuk, IuriiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeblinger, AksanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lingohr, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludwig, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hagel, Alexander F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schildberg, Claus W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veits, LotharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gyvyte, UgneUNSPECIFIEDorcid.org/0000-0002-1130-2472UNSPECIFIED
Weise, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schueller, VitaliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boehmer, Anne C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehlen, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuser, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofer, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, HaukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lordick, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malfertheiner, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moehler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pech, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vassos, NikolaosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodermann, ErnstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izbicki, Jakob R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruschewski, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ott, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumann, Ralf R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vieth, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangold, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gasenko, EvitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kupcinskas, LimasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimminger, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bujanda, LuisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sopena, FedericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinel, JesusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomson, ConchaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez-Aisa, AngelesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campo, RafaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geijo, FernandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collette, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Messerle, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gockel, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lippert, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ridwelski, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lanas, AngelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keller, GiselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knapp, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leja, MarcisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kupcinskas, JuozasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Gonzalez, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venerito, MarinoUNSPECIFIEDorcid.org/0000-0001-8581-0974UNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-171058
DOI: 10.1002/cam4.1719
Journal or Publication Title: Cancer Med.
Volume: 7
Number: 10
Page Range: S. 5057 - 5066
Date: 2018
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2045-7634
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STEM-CELL ANTIGEN; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; DUODENAL-ULCER; METAANALYSIS; VARIANTS; PRKAA1; ADENOCARCINOMA; POLYMORPHISMS; INFLAMMATIONMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17105

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