Open AccessEvidence for PTGER 4 , PSCA , and MBOAT 7 as risk genes for gastric cancer on the genome and transcriptome level
Author(s) -
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,
PérezAísa 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,
GarcíaGonzález Maria A.,
Venerito Marino,
Schumacher Johannes
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1719
Subject(s) - expression quantitative trait loci , transcriptome , genetics , biology , allele , quantitative trait locus , locus (genetics) , genome wide association study , gene , chromosome , population , single nucleotide polymorphism , gene expression , genotype , medicine , environmental health
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 −04 ) and on chromosome 8q24 at rs2585176 ( P = 1.09 × 10 −09 ). On chromosome 5p13 we found cis‐ eQTL effects with an upregulation of PTGER 4 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 MBOAT 7 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 PTGER 4 and PSCA as well as a downregulated expression of MBOAT 7 in gastric tissue as risk‐conferring GC pathomechanisms.