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 patients

BMC Cancer

Susanne Blank⁷  Sivaramakrishna Rachakonda⁶  Gisela Keller⁵  Wilko Weichert⁸  Florian Lordick¹  Rupert Langer⁴  Christoph Springfeld³  Thomas Bruckner²  Karen Becker⁵  Rajiv Kumar⁶  Katja Ott⁷ 

[1] University Cancer Center Leipzig (UCCL), Leipzig, Germany

[2] Medical Biometry, University of Heidelberg, Heidelberg, Germany

[3] National Center of Tumor Diseases, University of Heidelberg, Heidelberg, Germany

[4] Institute of pathology, University of Bern, Bern, Switzerland

[5] Institute of pathology, Technische Universitaet, Muenchen, Munich, Germany

[6] DKFZ, University of Heidelberg, Heidelberg, Germany

[7] Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany

[8] Institute of pathology, University of Heidelberg, Heidelberg, Germany

关键词: A1298C;    C677T;    Genetic polymorphisms;    Methylentetrahydrofolate reductase;    Folate metabolism;    Prognostic factors;    Esophagogastric adenocarcinoma;   

Others  :  859099
DOI  :  10.1186/1471-2407-14-58

 received in 2013-07-08, accepted in 2013-11-26,  发布年份 2014

【 摘 要 】

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 = 0.02, 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 6^th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7^th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), 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 6^th or 7^th 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.

【 授权许可】

   
2014 Blank et al.; licensee BioMed Central Ltd.

【 图 表 】

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