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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2011

01-09-2011 | Translational Research and Biomarkers

DNA Repair Gene and MTHFR Gene Polymorphisms as Prognostic Markers in Locally Advanced Adenocarcinoma of the Esophagus or Stomach Treated with Cisplatin and 5-Fluorouracil-Based Neoadjuvant Chemotherapy

Authors: Katja Ott, MD, P. Sivaramakrishna Rachakonda, PhD, Benjamin Panzram, PhD, Gisela Keller, MD, Florian Lordick, MD, Karen Becker, MD, Rupert Langer, MD, Markus Buechler, MD, Kari Hemminki, MD, Rajiv Kumar, PhD

Published in: Annals of Surgical Oncology | Issue 9/2011

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Abstract

Background

DNA repair plays an important role in chemoresistance to platinum-based therapy, and therefore polymorphisms in the genes may modulate therapeutic response. We assessed 12 polymorphisms in 7 DNA repair genes and 2 polymorphisms in the MTHFR gene for association with disease response and prognosis.

Methods

A total of 258 patients included in the study had adenocarcinoma of the esophagus (n = 114) or gastric cancer (n = 144), at stage cT3/4 and cM0, and had been treated with platinum-based neoadjuvant polychemotherapy. The patients were genotyped for polymorphisms in the XPC, XPD, XPG, APEX, XRCC1, NBS1, XRCC3, and MTHFR genes by the allelic discrimination method and the data correlated with various clinical parameters.

Results

None of the investigated polymorphisms was associated with histopathological response. XRCC3 polymorphisms rs861539 (P = 0.02) and rs861530 (P = 0.05) showed association with clinical response in gastric cancer. The variants in XRCC3 (rs861539, P = 0.05; rs1799794, P = 0.03) and MTHFR (rs1801131, P = 0.02) were associated with survival in esophageal and gastric cancer, respectively. In R0 resected patients, XRCC3 variants (rs861539, P = 0.04; rs861530, P = 0.02) in esophageal cancer, and XRCC3 (rs1799794, P = 0.02) and MTHFR (rs1801131, P = 0.005) in gastric cancer predicted survival. Cox regression revealed ypT category (P = 0.001) and lymphatic vessel invasion (P = 0.03) to be independent prognostic factors for esophageal cancer, and histopathological response (P = 0.01), MTHFR variant (rs1801131, P = 0.002), and ypN category (P = 0.02) to be prognostic factors for gastric cancer.

Conclusion

In gastric cancer patients, MTHFR variant (rs1801131) could serve as a potential prognostic marker. In esophageal cancer patients, none of the polymorphisms studied had conclusive results in multivariate analysis, although XRCC3 variant (rs861539) showed an effect on survival in Kaplan–Meier univariate analysis.
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Metadata
Title
DNA Repair Gene and MTHFR Gene Polymorphisms as Prognostic Markers in Locally Advanced Adenocarcinoma of the Esophagus or Stomach Treated with Cisplatin and 5-Fluorouracil-Based Neoadjuvant Chemotherapy
Authors
Katja Ott, MD
P. Sivaramakrishna Rachakonda, PhD
Benjamin Panzram, PhD
Gisela Keller, MD
Florian Lordick, MD
Karen Becker, MD
Rupert Langer, MD
Markus Buechler, MD
Kari Hemminki, MD
Rajiv Kumar, PhD
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1601-y

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