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

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 -