Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604759
Kurzvorträge
Ösophagus und Magen
Biomarker für Krankheitsrisiko und Prognose bei Ösophagus- und Magenkarzinom: Freitag, 15 September 2017, 10:10 – 11:30, Florenz/Forschungsforum 3
Georg Thieme Verlag KG Stuttgart · New York

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

T Hess
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
2   Life&Brain Research Center, Department of Genomics, Bonn, Deutschland
,
L Hamann
3   Institute for Microbiology and Hygiene, Charité University Medical Center Berlin, Berlin, Deutschland
,
YK Vashist
4   Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
,
K Butterbach
5   Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Heidelberg, Deutschland
,
T Schmidt
6   Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Deutschland
,
I Krasniuk
7   Department of General and Visceral Surgery, Municipal Hospital Solingen, Solingen, Deutschland
,
A Höblinger
8   Department of Internal Medicine I, Community Hospital Mittelrhein, Koblenz, Deutschland
,
P Lingohr
9   Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Deutschland
,
M Ludwig
10   Association for Oncological Studies (Gefos), Dortmund, Deutschland
,
AF Hagel
11   Department of Medicine I, Gastroenterology and Interventional Endoscopy, University of Erlangen, Erlangen, Deutschland
,
CW Schildberg
12   Department of Surgery, University of Erlangen, Erlangen, Deutschland
,
L Veits
13   Institute of Pathology, Clinic Bayreuth, Bayreuth, Deutschland
,
U Gyvyte
14   Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Litauen
,
MA Gonzalez-Carmona
15   Department of Internal Medicine I, University of Bonn, Bonn, Deutschland
,
SK Heinrichs
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
2   Life&Brain Research Center, Department of Genomics, Bonn, Deutschland
,
J Becker
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
2   Life&Brain Research Center, Department of Genomics, Bonn, Deutschland
,
F Lordick
16   University Cancer Center Leipzig (UCCL), University Hospital of Leipzig, Leipzig, Deutschland
,
P Malfertheiner
17   Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Deutschland
,
M Möhler
18   First Medical Clinic and Policlinic, University Medical Center, University of Mainz, Mainz, Deutschland
,
O Pech
19   Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Deutschland
,
E Rodermann
20   Association of Medical Practices in Hematology and Internal Oncology, Troisdorf, Deutschland
,
JR Izbicki
4   Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
,
M Kruschewski
7   Department of General and Visceral Surgery, Municipal Hospital Solingen, Solingen, Deutschland
,
K Ott
21   Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Deutschland
,
RR Schumann
3   Institute for Microbiology and Hygiene, Charité University Medical Center Berlin, Berlin, Deutschland
,
M Vieth
13   Institute of Pathology, Clinic Bayreuth, Bayreuth, Deutschland
,
E Mangold
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
,
L Kupcinskas
14   Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Litauen
,
H Brenner
5   Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Heidelberg, Deutschland
,
P Grimminger
22   Department of General, Visceral and Transplant Surgery, University Medical Center, Mainz, Deutschland
,
C Bruns
23   Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Deutschland
,
MW Büchler
24   Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Heidelberg, Deutschland
,
I Gockel
25   Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Deutschland
,
MM Nöthen
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
2   Life&Brain Research Center, Department of Genomics, Bonn, Deutschland
,
H Lippert
26   An-Institute for Quality Control in Surgery, Otto-von-Guericke University Hospital, Magdeburg, Deutschland
,
K Ridwelski
26   An-Institute for Quality Control in Surgery, Otto-von-Guericke University Hospital, Magdeburg, Deutschland
27   Department of Surgery, Hospital Magdeburg, Magdeburg, Deutschland
,
A Lanas
28   Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, University of Zaragoza, Zaragosa, Spanien
,
G Keller
29   Institute of Pathology, Technical University of Munich, München, Deutschland
,
M Knapp
30   Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Deutschland
,
M Leja
31   Digestive Disease Cencer GASTRO, Riga East University Hospital, Riga, Lettland
,
J Schumacher
1   Institute of Human Genetics, University of Bonn, Bonn, Deutschland
2   Life&Brain Research Center, Department of Genomics, Bonn, Deutschland
,
J Kupcinskas
14   Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Litauen
,
MA García-González
32   Instituto Aragonés de Ciencias de la Salud and Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spanien
,
M Venerito
17   Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2017 (online)

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Gastric carcinoma (GC) represents the fifth most common cancer type worldwide and the prognosis for affected patients remains to be poor. Effort on characterizing the somatic genomic landscape of GC revealed deep insights into the tumor biology. However, questions on interindividual differences in the risk for GC development remain to be solved. To elucidate germline risk variants and genes, GWAS in the Asian population were performed with success, but so far studies in patients of European origin are scarce.

To validate the Asian GWAS findings and to provide further functional insights we performed a fine mapping association study in 1,926 GC patients and 2,012 controls of European descent using high dense SNP marker sets on chromosome 5p13 and 8q24. We confirmed and refined the GC associations at both chromosomal regions. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10-04 (RR = 1.22)) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10-09 (RR = 1.34)). We next performed expression quantitative trait (eQTL) analyses using genomewide genotype and gastric transcriptome data from 143 individuals focusing on the GC associated makers. On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in risk allele carriers (P = 1.89 × 10-03). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in risk allele carriers (P = 6.73 × 10-09). In addition, we found trans-eQTL effects for 8q24 with an upregulation of MBOAT7 expression in risk allele carriers (P = 1.07 × 10-08).

In summary, we confirmed and refined the previously reported GC associations at 5p31 and 8q24. Moreover, our data imply the upregulation of PTGER4 and PSCA expression as risk-conferring GC pathomechanisms. In addition, our findings provide evidence that GC risk variants on 8q24 lead to an upregulation of MBOAT7, which might be involved in the pathophysiology of GC.