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

Heinrichs SKM, Hess T, Becker J, Hamann L, Vashist YK, Butterbach K, Schmidt T, Alakus H, Krasniuk I, Hoeblinger A, Lingohr P, Ludwig M, Hagel A, Schildberg CW, Veits L, Gyvyte U, Weise K, Schueller V, Boehmer AC, Schroeder J, Gehlen J, Kreuser N, Hofer S, Lang H, Lordick F, Malfertheiner P, Moehler M, Pech O, Vassos N, Rodermann E, Izbicki JR, Kruschewski M, Ott K, Schumann RR, Mangold E, Gasenko E, Kupcinskas L, Brenner H, Grimminger P, Bujanda L, Sopena F, Espinel J, Thomson C, Perez-Aisa A, Campo R, Geijo F, Collette D, Bruns C, Messerle K, Gockel I, Noethen MM, Lippert H, Ridwelski K, Lanas A, Keller G, Knapp M, Leja M, Kupcinskas J, Garcia-Gonzalez MA, Venerito M, Schumacher J, Vieth M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 7

Pages Range: 5057-5065

Journal Issue: 10

DOI: 10.1002/cam4.1719

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 ) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10 ). On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10 ). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10 ). 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 ). 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.

Authors with CRIS profile

Involved external institutions

CIBER Rare Diseases Spain (ES) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Lithuanian University of Health Sciences / Lietuvos sveikatos mokslų universitetas (LSMU) Lithuania (LT) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Universität zu Köln Germany (DE) University of Salamanca / Universidad de Salamanca Spain (ES) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Krankenhaus Barmherzige Brüder Germany (DE) Gemeinschaftsklinikum Mittelrhein Germany (DE) Hospital Obispo Polanco Spain (ES) Charité - Universitätsmedizin Berlin Germany (DE) Hospital Parc Tauli Spain (ES) Städtisches Klinikum Solingen Germany (DE) RoMed Kliniken - Kliniken der Stadt und des Landkreises Rosenheim GmbH Germany (DE) Klinikum Frankfurt (Oder) Germany (DE) Technische Universität München (TUM) Germany (DE) GefoS Gesellschaft für offene Systeme mbH Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Latvia Latvia (LV) Klinikum Bayreuth Germany (DE) Instituto de Investigación Sanitaria Aragón (IIS Aragón) Spain (ES) Ruprecht-Karls-Universität Heidelberg Germany (DE)

How to cite

APA:

Heinrichs, S.K.M., Hess, T., Becker, J., Hamann, L., Vashist, Y.K., Butterbach, K.,... Vieth, M. (2018). Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level. Cancer Medicine, 7(10), 5057-5065. https://doi.org/10.1002/cam4.1719

MLA:

Heinrichs, Sophie K. M., et al. "Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level." Cancer Medicine 7.10 (2018): 5057-5065.

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