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Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

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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 st...

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Bibliographic Details
Main Authors: Heinrichs, Sophie K. M. (Author) , Schmidt, Thomas (Author) , Brenner, Hermann (Author) , Butterbach, Katja (Author)
Format: Article (Journal)
Language:English
Published: October 2018
In: Cancer medicine
Year: 2018, Volume: 7, Issue: 10, Pages: 5057-5065
ISSN:2045-7634
DOI:10.1002/cam4.1719
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1002/cam4.1719
Verlag, kostenfrei, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198243/
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Author Notes:Sophie K.M. Heinrichs, Timo Hess, Jessica Becker, Lutz Hamann, Yogesh K. Vashist, Katja Butterbach, Thomas Schmidt, Hakan Alakus, Iurii Krasniuk, Aksana Höblinger, Philipp Lingohr, Monika Ludwig, Alexander F. Hagel, Claus W. Schildberg, Lothar Veits, Ugne Gyvyte, Katharina Weise, Vitalia Schüller, Anne C. Böhmer, Julia Schröder, Jan Gehlen, Nicole Kreuser, Sebastian Hofer, Hauke Lang, Florian Lordick, Peter Malfertheiner, Markus Moehler, Oliver Pech, Nikolaos Vassos, Ernst Rodermann, Jakob R. Izbicki, Martin Kruschewski, Katja Ott, Ralf R. Schumann, Michael Vieth, Elisabeth Mangold, Evita Gasenko, Limas Kupcinskas, Hermann Brenner, Peter Grimminger, Luis Bujanda, Federico Sopeña, Jesús Espinel, Concha Thomson, Ángeles Pérez‐Aísa, Rafael Campo, Fernando Geijo, Daniela Collette, Christiane Bruns, Katharina Messerle, Ines Gockel, Markus M. Nöthen, Hans Lippert, Karsten Ridwelski, Angel Lanas, Gisela Keller, Michael Knapp, Marcis Leja, Juozas Kupcinskas, Maria A. García‐González, Marino Venerito, Johannes Schumacher
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Summary: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 PTGER4 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 MBOAT7 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 PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk‐conferring GC pathomechanisms.
Item Description:Gesehen am 19.12.2018
Physical Description:Online Resource
ISSN:2045-7634
DOI:10.1002/cam4.1719

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