The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

Zhao, Tingting; Xu, Zhi; Gu, Dongying; Wu, Peng; Huo, Xinying; Wei, Xiaowei; Tang, Yongfei; Gong, Weida; He, Ming‐Liang; Chen, Jinfei

doi:10.1038/srep28019

Cited by 11 publications

(14 citation statements)

References 47 publications

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“…After screening the abstracts and texts, only 96 publications met the crude inclusion criteria and were selected for further assessment. Among them, five were excluded for containing survival data only 89 - 93 , seven lacked detailed data for further analysis 94 - 100 , eleven deviated from HWE 101 - 111 and one was a case-only study 112 . Ultimately, 72 publications 11 - 82 were included in the final meta-analysis ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Wang

et al. 2017

J. Cancer

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Methionine synthase reductase (MTRR) is a key regulatory enzyme involved in the folate metabolic pathway. Previous studies investigating the association of MTRR A66G polymorphism with cancer susceptibility reported inconclusive results. We performed the current meta-analysis to obtain a more precise estimation of the possible association. Published literatures were identified from PubMed, Embase and CBM databases up to October 2016. The strength of the association between the MTRR A66G polymorphism and cancer susceptibility was assessed using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Eighty five published studies with 32,272 cases and 37,427 controls were included in this meta-analysis. Pooled results indicated that the MTRR A66G polymorphism was associated with an increased overall cancer risk (homozygous model: OR = 1.08, 95% CI = 1.02-1.15, P = 0.009; recessive model: OR = 1.06, 95% CI = 1.00-1.12, P < 0.001 and allele comparison: OR = 1.03, 95% CI = 1.00-1.06, P < 0.001). Stratification analysis further indicated significant associations in head and neck cancer, Caucasians, Africans, and high quality studies. However, to avoid the “false-positive report”, the significant findings were assessed by the false-positive report probability (FPRP) test. Interestingly, the results of FPRP test revealed that the increased risk for MTRR A66G polymorphism among Africans need further validation due to the high probabilities of false-positive results. This meta-analysis suggests that the MTRR A66G polymorphism is associated with significantly increased cancer risk, a finding that needs to be confirmed in single large studies.

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Section: Resultsmentioning

confidence: 99%

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Wang

et al. 2017

J. Cancer

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“…In studies 18 - 21 directly comparing OS between GC patients with genotype CT+TT and those with genotype CC, only insignificant disadvantage of genotype CC over genotype CT+TT was discovered [(CT+TT)/CC HR=0.94, 95% CI: 0.73-1.22]. Other three studies 16 , 20 , 22 offered us results in another way: patients with genotype CC seem to own shorter OS than those with genotype TT. No significance existed as the HR of group TT versus CC was 0.85, 95% CI: [0.60, 1.20], and no significant results could be concluded when comparing OS of GC patients with genotype CT against genotype CC [CT/ CC HR=1.10, 95% CI: 0.77-1.57], either.…”

Section: Resultsmentioning

confidence: 97%

“…Comparison of OS between GC patients with genotype CT/TT and those with genotype CC when treated with 5-Fu based chemotherapy was exhibited directly in four articles 18 - 21 . Another three studies 16 , 20 , 22 presented results in a different way: OS of patients with genotype TT was compared with those with genotype CC and OS of patients with genotype CT was also compared against those with genotype CC. According to the statistical analysis procedure mentioned before, we processed these studies together to acquire a more comprehensive view of this question.…”

Section: Resultsmentioning

confidence: 99%

“…Stratifying by patients' ethnicities, the pooled HRs of GC patients with genotype CT+TT versus those with genotype CC were 0.92 (95%CI: 0.66-1.28) for studies conducted in Asian 18 - 21 and 1.19 (95%CI: 0.90-1.58) in European 16 , 22 . With stratified analysis that was based on the chemotherapy purpose, the pooled HRs of genotype CT+TT against CC were 1.03 (95%CI: 0.76-1.38) in the subgroup 'perioperative' 16 , 20 , 21 , 22 and 1.04 (95%CI: 0.67-1.61) in subgroup 'palliative' 18 , 19 . The results of subgroup analyses are listed in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

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A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis

Tang¹,

Yu²,

Jiang³

et al. 2018

J. Cancer

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5-fluorouracil (5-Fu) metabolism associated enzyme, methylenetetrahydrofolate reductase (MTHFR)'s polymorphism C677T can affect enzyme activity and a series of studies have been performed to examine the association of this MTHFR polymorphism with the clinical outcomes of gastric cancer (GC) patients treated with 5-Fu based chemotherapies. However, the results are inconsistent and inconclusive. Therefore, a more comprehensive summary like meta-analysis on this topic is needed. We performed a systematic literature search of PubMed and Embase up to May 20, 2017. Researches exploring MTHFR polymorphisms C677T's relationship with the clinical outcomes (response rate, overall survival and toxicity) of GC patients treated with 5-Fu based chemotherapy were included. The association was measured by odds ratios (ORs) or hazard ratios (HRs) combined with their 95% confidence intervals (CIs) using random/fixed effects model according to the studies' heterogeneity. Subgroup, sensitivity and publication bias analyses were conducted. Thirteen studies were finally included in this meta-analysis. No significant association was found between response rate [TT/ (CC+CT) OR=1.31, 95% CI: 0.62-2.76] or overall survival [(CT+TT)/CC HR=1.05, 95% CI: 0.86-1.26; TT/(CT+CC) HR=1.48, 95% CI: 0.53-4.15] and MTHFR polymorphism C677T. However, GC patients with CC or CT genotype tended to experience less severe hematologic toxicity than those with TT genotype [(CC+CT)/TT OR=0.66, 95% CI: 0.48-0.91]. In conclusion, MTHFR C677T polymorphism predicts severe hematologic toxicity in GC patients receiving 5-Fu based chemotherapy, but not the efficiency.

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“…The mice were sacrificed before the metastasis analysis. 54 , 59 The metastases were enumerated using a dissecting microscope. To estimate the tumor volume, the diameter of each metastatic lesion was measured, and the volume of each tumor was calculated on the assumption that the tumors were spherical.…”

Section: Methodsmentioning

confidence: 99%

Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma

Dong

Chen

et al. 2018

Sig Transduct Target Ther

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Tbx3, a transcriptional repressor, is essential in the organogenesis of vertebrates, stem cell self-renewal and differentiation, and the carcinogenesis of multiple tumor types. However, the mechanism by which Tbx3 participates in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown. In this study, we show that Tbx3 was dramatically upregulated in clinical HCC samples and that elevated expression of Tbx3 promoted cancer progression. To determine the underlying mechanism, systematic glycine scan mutagenesis and deletion assays were performed. We identified two critical motifs, 585LFSYPYT591 and 604HRH606, that contribute to the repression of transcriptional activity. These motifs are also essential for Tbx3 to promote cell migration and metastasis both in vitro and in vivo via the suppression of E-cadherin expression. More importantly, Tbx3 directly interacts with HDAC5 via these motifs, and an HDAC inhibitor blocks Tbx3-mediated cell migration and the downregulation of E-cadherin in HCC. As Tbx3 is involved in the carcinogenesis of multiple types of human cancers, our findings suggest an important target for anti-cancer drug development.

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The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

Cited by 11 publications

References 47 publications

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious Hematologic Toxicity but Not Prognosis

Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma

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