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

Zhao Y, Li X, Kong X - Med. Sci. Monit. (2015)

Bottom Line: However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response.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.Further well-designed, larger-scale epidemiological studies are needed to validate our results.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Forest plot for the association of MTHFR C677T polymorphism and the tumor response to pRCT stratified by the responder definition.
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f2-medscimonit-21-3068: Forest plot for the association of MTHFR C677T polymorphism and the tumor response to pRCT stratified by the responder definition.

Mentions: We firstly analyzed the association of MTHFR C677T with the response to pRCT under 5 genetic models. Overall, the C677T polymorphism was correlated with the response to pRCT in recessive model (CC vs. CTTT, OR=1.426(1.074–1.894), P=0.014, Table 2), but not in allele model, homozygote model, heterozygote model, or dominant model. In subgroup analysis according to cancer type, a significant association was also found in recessive model in rectal cancer (CC vs. CTTT, OR=1.483(1.102–1.996), P=0.009, Table 2), but no significant association existed in other genetic models. When the subgroup analysis was performed according to responder definition, a significant association was only found in recessive model in TRG 1–2 vs. 3–5 group (CC vs. CTTT, OR=1.423(1.046–1.936), P=0.025, Table 2, Figure 2). The results suggest that patients (especially those with rectal cancer) carrying CC genotype might benefit from pRCT compared with CT or TT carriers. The association between MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms and the response to pRCT was also examined; however, no significant association was identified in overall or subgroup analyses, only a trend that EGFR short (S) CA repeat might harbor a unfavorable role in response to pRCT in overall analysis (S vs. L, OR=0.639(0.397–1.030), P=0.066, Table 2, Figure 4).


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

Zhao Y, Li X, Kong X - Med. Sci. Monit. (2015)

Forest plot for the association of MTHFR C677T polymorphism and the tumor response to pRCT stratified by the responder definition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4608643&req=5

f2-medscimonit-21-3068: Forest plot for the association of MTHFR C677T polymorphism and the tumor response to pRCT stratified by the responder definition.
Mentions: We firstly analyzed the association of MTHFR C677T with the response to pRCT under 5 genetic models. Overall, the C677T polymorphism was correlated with the response to pRCT in recessive model (CC vs. CTTT, OR=1.426(1.074–1.894), P=0.014, Table 2), but not in allele model, homozygote model, heterozygote model, or dominant model. In subgroup analysis according to cancer type, a significant association was also found in recessive model in rectal cancer (CC vs. CTTT, OR=1.483(1.102–1.996), P=0.009, Table 2), but no significant association existed in other genetic models. When the subgroup analysis was performed according to responder definition, a significant association was only found in recessive model in TRG 1–2 vs. 3–5 group (CC vs. CTTT, OR=1.423(1.046–1.936), P=0.025, Table 2, Figure 2). The results suggest that patients (especially those with rectal cancer) carrying CC genotype might benefit from pRCT compared with CT or TT carriers. The association between MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms and the response to pRCT was also examined; however, no significant association was identified in overall or subgroup analyses, only a trend that EGFR short (S) CA repeat might harbor a unfavorable role in response to pRCT in overall analysis (S vs. L, OR=0.639(0.397–1.030), P=0.066, Table 2, Figure 4).

Bottom Line: However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response.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.Further well-designed, larger-scale epidemiological studies are needed to validate our results.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus