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@ARTICLE{Heinrichs:137570,
author = {S. K. M. Heinrichs and T. Hess and J. Becker and L. Hamann
and Y. K. Vashist and K. Butterbach$^*$ and T. Schmidt and
H. Alakus and I. Krasniuk and A. Höblinger and P. Lingohr
and M. Ludwig and A. F. Hagel and C. W. Schildberg and L.
Veits and U. Gyvyte and K. Weise and V. Schüller and A. C.
Böhmer and J. Schröder and J. Gehlen and N. Kreuser and S.
Hofer and H. Lang and F. Lordick and P. Malfertheiner and M.
Moehler and O. Pech and N. Vassos and E. Rodermann and J. R.
Izbicki and M. Kruschewski and K. Ott and R. R. Schumann and
M. Vieth and E. Mangold and E. Gasenko and L. Kupcinskas and
H. Brenner$^*$ and P. Grimminger and L. Bujanda and F.
Sopeña and J. Espinel and C. Thomson and Á. Pérez-Aísa
and R. Campo and F. Geijo and D. Collette and C. Bruns and
K. Messerle and I. Gockel and M. M. Nöthen and H. Lippert
and K. Ridwelski and A. Lanas and G. Keller and M. Knapp and
M. Leja and J. Kupcinskas and M. A. García-González and M.
Venerito and J. Schumacher},
title = {{E}vidence for {PTGER}4, {PSCA}, and {MBOAT}7 as risk genes
for gastric cancer on the genome and transcriptome level.},
journal = {Cancer medicine},
volume = {7},
number = {10},
issn = {2045-7634},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2018-01450},
pages = {5057-5065},
year = {2018},
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 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.},
cin = {C070 / G110 / L101},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30191681},
doi = {10.1002/cam4.1719},
url = {https://inrepo02.dkfz.de/record/137570},
}