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MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports

Yue Zhao, Xingde Li, Xiangjun Kong

Department of Radiation Therapy, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland)

Med Sci Monit 2015; 21:3068-3076

DOI: 10.12659/MSM.895433

Available online:

Published: 2015-10-12

BACKGROUND: Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive.
MATERIAL AND METHODS: A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models.
RESULTS: A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074–1.894), P=0.014), rectal cancer (OR=1.483(1.102–1.996), P=0.009), and TRG 1–2 vs. 3–5 group (OR=1.423(1.046–1.936), P=0.025), while other polymorphism including MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms exerted significant association under all genetic models in overall analysis or subgroup analysis.
CONCLUSIONS: MTHFR C677T might be correlated with the tumor response to pRCT. Further well-designed, larger-scale epidemiological studies are needed to validate our results.

Keywords: Adult, Alleles, Antineoplastic Agents - therapeutic use, Biomarkers, Tumor, Chemoradiotherapy - methods, Chemotherapy, Adjuvant, Combined Modality Therapy, Methylenetetrahydrofolate Reductase (NADPH2) - genetics, Neoplasms - surgery, Odds Ratio, Polymorphism, Single Nucleotide, preoperative period, Receptor, Epidermal Growth Factor - genetics, Rectal Neoplasms - surgery