A retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patien

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• 作者：Susanne Blank (14)
  Sivaramakrishna Rachakonda (15)
  Gisela Keller (16)
  Wilko Weichert (17)
  Florian Lordick (18)
  Rupert Langer (19)
  Christoph Springfeld (20)
  Thomas Bruckner (21)
  Karen Becker (16)
  Rajiv Kumar (15)
  Katja Ott (14)
  
• 关键词：Esophagogastric adenocarcinoma ; Prognostic factors ; Folate metabolism ; Methylentetrahydrofolate reductase ; Genetic polymorphisms ; C677T ; A1298C
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：385 KB
• 作者单位：Susanne Blank (14)
  Sivaramakrishna Rachakonda (15)
  Gisela Keller (16)
  Wilko Weichert (17)
  Florian Lordick (18)
  Rupert Langer (19)
  Christoph Springfeld (20)
  Thomas Bruckner (21)
  Karen Becker (16)
  Rajiv Kumar (15)
  Katja Ott (14)
  
  14. Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany
  15. DKFZ, University of Heidelberg, Heidelberg, Germany
  16. Institute of pathology, Technische Universitaet, Muenchen, Munich, Germany
  17. Institute of pathology, University of Heidelberg, Heidelberg, Germany
  18. University Cancer Center Leipzig (UCCL), Leipzig, Germany
  19. Institute of pathology, University of Bern, Bern, Switzerland
  20. National Center of Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  21. Medical Biometry, University of Heidelberg, Heidelberg, Germany
  
• ISSN：1471-2407

文摘

Background Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. Methods 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Results Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p--.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p--.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p--.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. Conclusions The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with neoadjuvantly treated gastric adenocarcinomas (according to both UICC 6th or 7th definitions for gastric cancer) but not in AEG I nor in primarily resected patients, which confirms the impact of this enzyme on chemotherapy associated outcome.