Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level
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Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level. / Heinrichs, Sophie K M; Hess, Timo; Becker, Jessica; Hamann, Lutz; Vashist, Yogesh K; Butterbach, Katja; Schmidt, Thomas; Alakus, Hakan; Krasniuk, Iurii; Höblinger, Aksana; Lingohr, Philipp; Ludwig, Monika; Hagel, Alexander F; Schildberg, Claus W; Veits, Lothar; Gyvyte, Ugne; Weise, Katharina; Schüller, Vitalia; Böhmer, Anne C; Schröder, 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; Sopeña, Federico; Espinel, Jesús; Thomson, Concha; Pérez-Aísa, Ángeles; Campo, Rafael; Geijo, Fernando; Collette, Daniela; Bruns, Christiane; Messerle, Katharina; Gockel, Ines; Nöthen, Markus M; Lippert, Hans; Ridwelski, Karsten; Lanas, Angel; Keller, Gisela; Knapp, Michael; Leja, Marcis; Kupcinskas, Juozas; García-González, Maria A; Venerito, Marino; Schumacher, Johannes.
in: CANCER MED-US, Jahrgang 7, Nr. 10, 10.2018, S. 5057-5065.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level
AU - Heinrichs, Sophie K M
AU - Hess, Timo
AU - Becker, Jessica
AU - Hamann, Lutz
AU - Vashist, Yogesh K
AU - Butterbach, Katja
AU - Schmidt, Thomas
AU - Alakus, Hakan
AU - Krasniuk, Iurii
AU - Höblinger, Aksana
AU - Lingohr, Philipp
AU - Ludwig, Monika
AU - Hagel, Alexander F
AU - Schildberg, Claus W
AU - Veits, Lothar
AU - Gyvyte, Ugne
AU - Weise, Katharina
AU - Schüller, Vitalia
AU - Böhmer, Anne C
AU - Schröder, Julia
AU - Gehlen, Jan
AU - Kreuser, Nicole
AU - Hofer, Sebastian
AU - Lang, Hauke
AU - Lordick, Florian
AU - Malfertheiner, Peter
AU - Moehler, Markus
AU - Pech, Oliver
AU - Vassos, Nikolaos
AU - Rodermann, Ernst
AU - Izbicki, Jakob R
AU - Kruschewski, Martin
AU - Ott, Katja
AU - Schumann, Ralf R
AU - Vieth, Michael
AU - Mangold, Elisabeth
AU - Gasenko, Evita
AU - Kupcinskas, Limas
AU - Brenner, Hermann
AU - Grimminger, Peter
AU - Bujanda, Luis
AU - Sopeña, Federico
AU - Espinel, Jesús
AU - Thomson, Concha
AU - Pérez-Aísa, Ángeles
AU - Campo, Rafael
AU - Geijo, Fernando
AU - Collette, Daniela
AU - Bruns, Christiane
AU - Messerle, Katharina
AU - Gockel, Ines
AU - Nöthen, Markus M
AU - Lippert, Hans
AU - Ridwelski, Karsten
AU - Lanas, Angel
AU - Keller, Gisela
AU - Knapp, Michael
AU - Leja, Marcis
AU - Kupcinskas, Juozas
AU - García-González, Maria A
AU - Venerito, Marino
AU - Schumacher, Johannes
N1 - © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
KW - Acyltransferases/genetics
KW - Antigens, Neoplasm/genetics
KW - Case-Control Studies
KW - Chromosome Mapping/methods
KW - Chromosomes, Human, Pair 5/genetics
KW - Chromosomes, Human, Pair 8/genetics
KW - Female
KW - GPI-Linked Proteins/genetics
KW - Gene Expression Profiling/methods
KW - Gene Expression Regulation, Neoplastic
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Male
KW - Membrane Proteins/genetics
KW - Neoplasm Proteins/genetics
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Receptors, Prostaglandin E, EP4 Subtype/genetics
KW - Stomach Neoplasms/genetics
U2 - 10.1002/cam4.1719
DO - 10.1002/cam4.1719
M3 - SCORING: Journal article
C2 - 30191681
VL - 7
SP - 5057
EP - 5065
JO - CANCER MED-US
JF - CANCER MED-US
SN - 2045-7634
IS - 10
ER -