Universität zu Köln

Jung, Jin-On ORCID: 0000-0001-6121-0114, Wirsik, Naita Maren, Nienhueser, Henrik, Peters, Leila, Mueller-Stich, Beat Peter, Hess, Timo, Schueller, Vitalia, Schumacher, Johannes and Schmidt, Thomas ORCID: 0000-0002-7166-3675 (2022). Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery. Ann. Surg. Oncol., 29 (2). S. 1453 - 1463. NEW YORK: SPRINGER. ISSN 1534-4681

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Abstract

Background Gastric and esophageal cancers are malignant diseases with rising importance in Western countries. To improve oncologic outcome after surgery, it is essential to understand the relevance of germline mutations. The aim of the study was to identify and distinguish clinically relevant single-nucleotide polymorphisms (SNPs). Patients and Methods In total, 190 patients with curative oncological resections of gastric and distal esophageal adenocarcinomas at Heidelberg University Hospital were eligible for this study. Outcome differences were determined for each SNP by analysis of clinical variables, survival, and mRNA expression levels. Results Significant survival differences were found on univariate analysis for usual prognostic variables (such as pTNM) and for six SNPs. On multivariate survival analysis, the SNPs rs12268840 (intron variant of MGMT, p = 0.045) and rs9972882 (intron variant of STARD3 and eQTL of PGAP3, p = 0.030) were independent and significant survival predictors along with R status and pT/pN category. Group TT of rs12268840 had the highest rate of second primary carcinoma (30.4%, p = 0.0003), lowest expression of MGMT based on cis-eQTL analysis in normal gastroesophageal tissue (p = 1.99 x 10(-17)), and worst oncologic outcome. Group AA of rs9972882 had the highest rate of distant metastases pM1 (42.9%, p = 0.0117), highest expression of PGAP3 (p = 1.29 x 10(-15)), and worst oncologic outcome. Conclusions Two intron variant SNPs of MGMT and STARD3 were identified that were significant survival predictors and may influence tumor biology. The data indicate that DNA methylation (MGMT) and malfunction of GPI anchoring (PGAP3) are distinct mechanisms that are relevant for tumor progression and relapse.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jung, Jin-On UNSPECIFIED orcid.org/0000-0001-6121-0114 UNSPECIFIED Wirsik, Naita Maren UNSPECIFIED UNSPECIFIED UNSPECIFIED Nienhueser, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Leila UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller-Stich, Beat Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schueller, Vitalia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Thomas UNSPECIFIED orcid.org/0000-0002-7166-3675 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586625
DOI:	10.1245/s10434-021-10771-y
Journal or Publication Title:	Ann. Surg. Oncol.
Volume:	29
Number:	2
Page Range:	S. 1453 - 1463
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1534-4681
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; GASTRIC-CANCER; ESOPHAGEAL ADENOCARCINOMA; SUSCEPTIBILITY LOCI; RISK; GENES; POLYMORPHISMS; METHYLATION; EXPRESSION; ERBB2 Multiple languages Oncology; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58662