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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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany

    Katja Ott MD, Benjamin Panzram PhD & Markus Buechler MD

  2. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany

    P. Sivaramakrishna Rachakonda PhD, Kari Hemminki MD & Rajiv Kumar PhD

  3. Department of Pathology, Klinikum rechts der Isar, Technische Universität, Munich, Germany

    Gisela Keller MD, Karen Becker MD & Rupert Langer MD

  4. Klinikum Braunschweig, Braunschweig and Hannover Medical School, Hannover, Germany

    Florian Lordick MD

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  1. Katja Ott MD
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  2. P. Sivaramakrishna Rachakonda PhD
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  3. Benjamin Panzram PhD
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  4. Gisela Keller MD
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Correspondence to P. Sivaramakrishna Rachakonda PhD.

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The first two authors contributed equally to this work.

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Ott, K., Rachakonda, P.S., Panzram, B. et al. 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. Ann Surg Oncol 18, 2688–2698 (2011). https://doi.org/10.1245/s10434-011-1601-y

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  • DOI: https://doi.org/10.1245/s10434-011-1601-y

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