Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis

Xu, Lingyan; Qin, Zhiqiang; Wang, Feng; Si, Shuhui; Li, Lele; Lin, Peinan; Han, Xiao; Cai, Xiaoxiao; Yang, Haiwei; Gu, Yanhong

doi:10.1042/bsr20170917

Cited by 11 publications

(11 citation statements)

References 98 publications

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“…The MTHFR polymorphisms result in decreased enzyme activity and then low levels of plasma folate and high homocysteine. Folate takes part in various biochemical reactions to provide or accept one-carbon units [14]. Folate deficiency is likely to develop into cancer, possibly due to DNA structural defects [15].…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase polymorphism and capecitabine-induced toxicity in patients with gastric cancer

Xie¹,

Wang²,

Zhang³

2020

Trop. J. Pharm Res

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Purpose: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphism on toxicity in gastric cancer (GC) patients treated with capecitabine. Methods: One hundred and twenty-six GC patients were treated with capecitabine in the study. DNA from GC patients was genotyped for MTHFR A1298C using direct sequencing. Toxicity evaluations were graded. Clinical response was assessed. Results: In 87.3 % of the patients, capecitabine toxicity was observed. As for MTHFR A1298C polymorphism, 55.6 % patients who exhibited it were associated with reduced MTHFR activity. MTHFR A1298C was associated with capecitabine-related toxicity (p = 0.008); in addition, MTHFR A1298C was significantly associated with gastrointestinal toxicity (p = 0.026), but not with other types of toxicity. Conclusion: The findings suggest that MTHFR A1298C may be useful for predicting toxicity in GC patients receiving capecitabine treatment, especially gastrointestinal toxicity. Keywords: MTHFR, Polymorphism, Gastric cancer, Toxicity

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Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase polymorphism and capecitabine-induced toxicity in patients with gastric cancer

Xie¹,

Wang²,

Zhang³

2020

Trop. J. Pharm Res

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“…In 2011, Zacho, J. et al enrolled 75,000 cases and 93,000 controls for a meta-analysis of the association between the MTHFR rs1801133 polymorphism and overall cancer susceptibility and found that the TT genotype of MTHFR rs1801133 was associated with a decreased risk in CRC patients with lifelong hyperhomocysteinemia and hence hypomethylation [33]. Recently, data from another updated meta-analysis with 37,049 cases and 52,444 controls from 91 case-control studies suggested that the MTHFR rs1801133 polymorphism was related to a reduced risk of CRC, particularly in the Asian population [34]. These data supported the protective effect of MTHFR polymorphism, especially rs1801133, on CRC risk.…”

Section: Discussionmentioning

confidence: 99%

“…Third, hyperplastic and adenomatous polyps have complex and different etiologies. As a genetic effect of MTHFR rs1801133 and rs1801131 polymorphisms has been suggested in the susceptibility to colorectal cancer [6, 11, 33, 34], additional confounding factors such as smoking, drinking, age, sex, and patient features should be adjusted for further investigation of the MTHFR variants in the malignant conversion from colorectal polyp.…”

Section: Discussionmentioning

confidence: 99%

Genetic impact of methylenetetrahydrofolate reductase (MTHFR) polymorphism on the susceptibility to colorectal polyps: a meta-analysis

et al. 2019

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Background There are several studies with inconsistent conclusions regarding the association between the rs1801133 and rs1801131 polymorphisms within the MTHFR (methylenetetrahydrofolate reductase) gene and colorectal polyp risk. This discrepancy led us to assess the genetic impact of the two polymorphisms on the susceptibility to colorectal polyps. Methods A meta-analysis was carried out for quantitative synthesis. According to the inclusion/exclusion criteria, we retrieved, screened and selected all published articles related to colorectal polyps and the MTHFR rs1801133 and rs1801131 polymorphisms. The P value of association test, RRs (risk ratios) and 95% CIs (confidence intervals) were mainly produced. Results A total of twenty-three case-control studies were included from twenty-two eligible articles. Pooling the results of both rs1801133 and rs1801131 polymorphisms in the overall population suggested a nonsignificant association between colorectal polyp cases and controls, in that all P values in the test of association were larger than 0.05. Nevertheless, pooling results in the “UK” subgroup of rs1801131, comprising five studies (1257 cases/1407 controls), indicated an elevated risk in colorectal polyp cases in comparison with controls, under the genetic models of CC vs. AA ( P = 0.032, RR = 1.27, 95% CIs = 1.02, 1.57) and CC vs. AA+AC ( P = 0.036, RR = 1.27, 95% CIs = 1.02, 1.60). Conclusion The C/C genotype of MTHFR rs1801131 is more likely to be a genetic risk factor for colorectal polyps in the UK region, although this finding should be verified with a larger sample size. Electronic supplementary material The online version of this article (10.1186/s12881-019-0822-y) contains supplementary material, which is available to authorized users.

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“…However, the effects of MTHFR polymorphism on cancer risk were controversial. Recent published meta-analysis demonstrated MTHFR C677T polymorphism has an increased risk of breast and esophageal cancer, while a decreased risk of colorectal cancer was detected[ 9 – 11 ]. Thus, MTHFR polymorphism might play various roles in different type of cancers.…”

Section: Discussionmentioning

confidence: 99%

“…However, in view of the available data, studies on the association between MTHFR C677T polymorphisms and cancer risk have yielded mixed results. Some reports indicated that T allele could protect against cancer, while another studies revealed that subjects carrying T allele have increased susceptibility to cancer[ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: A systematic review and meta-analysis

Jiao

Chang

2018

PLoS ONE

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A consensus has not been reached regarding the association of MTHFR gene polymorphism and susceptibility to oral squamous cell carcinoma (OSCC). We performed a meta-analysis to better evaluate the association between MTHFR C677T, A1298C polymorphism and OSCC risk. The studies regarding the association of MTHFR C677T, A1298C polymorphisms and OSCC were identified in PubMed and EMBASE and Google Scholar. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect model. The associations between MTHFR polymorphisms and OSCC risk were assessed under the dominant, recessive and additive models. A collective total of 1539 OSCC patients and 2131 normal controls were included across 13 studies. The minor T allele of MTHFR C677T was significantly associated with the increased risk of OSCC development(OR = 1.35, 95%CI 1.04–1.76). Individuals carrying the ‘‘T” allele (TT+CT) had a nearly 43% increased risk for OSCC development when compared with CC (OR = 1.43, 95%CI 1.02–1.99). Under additive model, the results also showed that individuals with CT or TT genotype were more susceptible to OSCC than CC (OR = 1.45, 95%CI 1.02–2.08; OR = 1.79, 95%CI 1.28–2.50; respectively). The subgroup analysis by ethnicity revealed that significant difference in C677T allele distribution could be observed in European (OR = 1.33, 95%CI 1.02–1.75) rather than Asian (OR = 1.59, 95%CI 0.91–2.78). No significant association of MTHFR A1298C polymorphism and OSCC risk could be observed. The present study revealed that T allele and TT genotype of MTHFR C677T polymorphism were significantly associated with the increased risk of OSCC development.

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Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis

Cited by 11 publications

References 98 publications

Methylenetetrahydrofolate reductase polymorphism and capecitabine-induced toxicity in patients with gastric cancer

Methylenetetrahydrofolate reductase polymorphism and capecitabine-induced toxicity in patients with gastric cancer

Genetic impact of methylenetetrahydrofolate reductase (MTHFR) polymorphism on the susceptibility to colorectal polyps: a meta-analysis

The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: A systematic review and meta-analysis

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