Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran’s Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger’s test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92 1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.     

Association between MTHFR C677T Polymorphism and Risk of Prostate Cancer: Evidence from 22 Studies with 10,832 Cases and 11,993 Controls

Background: The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved infolate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim ofthis study was to investigate the association between MTHFR C677T polymorphism and prostate cancer byperforming a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched forcase-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer.Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. Results: A total of 22independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed thatthere was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer underall five genetic models. There was also no obvious association between MTHFR C677T polymorphism andrisk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphismwas associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95%CI =1.121-1.506, P=0.001, Pheterogeneity =0.120, I2=45%), additive genetic model (CC vs TT: OR =1.925, 95 %CI= 1.340-2.265, P=0.00, Pheterogeneity =0.587, I2=0.00%), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI=1.233-2.367, P=0.001, Pheterogeneity =0.716, I2=0.00%), and heterozygote genetic model (CT vs TT: OR=2.193, 95% CI =1.510-3.186, P=0.000, Pheterogeneity =0.462, I2=0.00%). Conclusions: These results suggest that the MTHFRC677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence inpopulations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostatecancer development in Asians.     

The Methylenetetrahydrofolate Reductase C677T Polymorphism and Breast Cancer Risk in Asian Populations

Background: Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway andseveral studies have pointed to association between the MTHFR C677T polymorphism and breast cancer risk.Although significant association was observed in some studies, in others no clear link could be established.Objective: A meta-analysis of published Asian case control studies was therefor carried out to shed further lighton any C677T breast cancer association. Materials and Methods: PubMed, Springer Link, Google Scholar andElsevier databases were searched for case control studies of associations between MTHFR C677T polymorphismand breast cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess theassociation. A total of 36 studies including 8,040 cases and 10,008 controls were included in the present metaanalysis.Results: Overall, a significantly elevated breast cancer risk was associated with the T allele and TTgenotype in homozygote comparison and dominant genetic models when all studies were pooled into the metaanalysis(T vs C (allele contrast model): OR=1,23, 95%CI=1.13-1.37, p=0.000 ; TT vs CC(homozygote model):OR=1.38, 95%CI=1.16-1.63, p=0.0003; TT+CT vs CC (dominant model): OR=1.12, 95%CI=1.01-1.23, p=0.02).Conclusions: The present meta-analysis strongly suggested a significant association between the MTHFR C677Tpolymorphism and risk of breast cancer in Asian populations.     

Methylenetetrahydrofolate reductase C677T polymorphism and cervical cancer risk: a meta-analysis

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate,and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. Method: Weperformed a meta-analysis of all relevant case-control studies that examined any association between the C677Tpolymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals(CIs) to assess links. Results: Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls wereincluded. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associatedwith the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TTvs. CC, OR = 1.37, 95%CI 1.00-1.87, P = 0.050; for TT vs. TC+CC: OR = 1.34, 95%CI 1.01-1.77, P = 0.039).However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer riskin the other populations. Conclusion: The MTHFR C677T polymorphism is associated with cervical cancer riskin Asians, while any possible link in the Caucasian population needs further studies.     

Methylenetetrahydrofolate Reductase Polymorphisms and Susceptibility to Esophageal Cancer in Chinese Populations:a Meta-analysis

Although many epidemiologic studies investigated the methylenetetrahydrofolate reductase (MTHFR)polymorphisms and their associations with esophageal cancer, definite conclusions could not be drawn. To clarifythe effects of MTHFR polymorphisms on the risk of esophageal cancer, a meta-analysis was here performed inChinese populations. A total of 16 studies including 3,040 cases and 4,127 controls were involved in this metaanalysis.Overall, significant associations were found between the MTHFR C677T polymorphism and esophagealcancer risk when all studies in Chinese populations were pooled into the meta-analysis (T vs. C, OR = 1.19, 95%CI = 1.06–1.34; TT vs. CC, OR = 1.35, 95% CI = 1.07–1.70; TT+ CT vs. CC, OR = 1.29, 95% CI = 1.08–1.54;TT vs. CC + CT, OR = 1.19, 95% CI = 1.03–1.37). In subgroup analyses stratified by ethnicity and source ofcontrols, the same results were found in Kazakh (TT vs. CC, OR = 1.38, 95% CI = 1.02-1.87; TT + CT vs. CC,OR = 1.50, 95% CI = 1.03-2.18), in not stated populations (T vs. C, OR = 1.24, 95% CI = 1.08-1.42; TT vs. CC,OR = 1.47, 95% CI = 1.10-1.96; TT + CT vs. CC, OR = 1.30, 95% CI = 1.05-1.60; TT vs. CC + CT, OR = 1.32,95% CI = 1.12-1.56), and in hospital-based studies (T vs. C, OR = 1.34, 95% CI = 1.19-1.51; TT vs. CC, OR =1.81, 95% CI = 1.37-2.39; TT + CT vs. CC, OR = 1.51, 95% CI = 1.26-1.83; and TT vs. CC + CT, OR = 1.39,95% CI = 1.13-1.70). In conclusion, this meta-analysis provides evidence that the MTHFR C677T polymorphismcontributes to esophageal cancer development in Chinese populations.     

MTHFR基因C667T位点多态性与亚洲人群乳腺癌易感性的Meta分析

目的:采用Meta分析的方法定量评价亚甲基四氢叶酸还原酶（MTHFR）基因C667T位点的多态性与亚洲人群乳腺癌易感性的关系。方法:计算机检索PubMed、Web of Science、中国生物医学文献数据库、CNKI、重庆维普和万方数据库,搜索有关MTHFR基因C667T位点的多态性与亚洲人群乳腺癌易感性的研究,检索时间截止2017年2月。采用Stata 12.0软件进行统计分析。结果:共纳入24篇病例对照研究,共计7 268例乳腺癌患者,9 223例健康对照。Meta分析结果显示:MTHFR基因C667T位点的多态性均与亚洲人群乳腺癌易感性有相关性［CC vs CT:OR=0.70,95%CI（0.60,0.83）,P=0.001;CT vs TT:OR=0.87,95%CI（0.79,0.96）,P=0.05;CC vs TT:OR=0.79,95%CI（0.72,0.88）,P=0.002;CT+TT vs CC:OR=0.81,95%CI（0.76,0.87）,P=0.001;CC+CT vs TT:OR=0.85,95%CI（0.77,0.93）,P=0.003］。结论:MTHFR基因C667T位点的多态性增加了亚洲人群乳腺癌的易感性。     

Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotidesneeded for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lungcancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial orinconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and GoogleScholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association.Results: Overall, no significant association was detected between the MTHFR C677T polymorphism and LCrisk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increasednon-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TTvs. CC: OR = 1.24, 95%CI = 1.09-1.41; TC vs. CC: OR = 1.11, 95%CI = 1.03-1.20 and TT+TC vs. CC: OR =1.09, 95%CI = 1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreasedLC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677Tnull genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studieswith large sample sizes are warranted to further evaluate this association in more detail.     

Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis

The associations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and methotrexate (MTX)-induced toxicities in patients with acute lymphoblastic leukemia (ALL) have been evaluated in various populations, with the results remained conflicting. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure were searched until 21 September 2011 to identify eligible studies. A total of 14 studies were included, with all studies investigating MTHFR C677T polymorphism while nine of them investigating MTHFR A1298C polymorphism only. Results suggested that MTHFR C677T polymorphism was associated with significantly increased risk of MTX-induced toxicity, specifically liver toxicity (TT/CT vs. CC: odds ratio (OR)?=?1.70, 95?% confidence interval (CI)?=?1.05?C2.75), myelosuppression (TT vs. CT/CC: OR?=?2.82, 95?%CI?=?1.25?C6.34), oral mucositis (TT/CT vs. CC: OR?=?3.68, 95?%CI?=?1.73?C7.85), gastrointestinal toxicity (TT/CT vs. CC: OR?=?2.36, 95?%CI?=?1.36?C4.11), and skin toxicity (T vs. C: OR?=?2.26, 95?%CI?=?1.07?C4.74). MTHFR A1298C polymorphism was found to be associated with decreased risk of skin toxicity (CC/AC vs. AA: OR?=?0.11, 95?%CI?=?0.01?C0.85). Genotyping of MTHFR polymorphism, C677T particularly, prior to treatment for ALL is likely to be useful with the aim of tailoring MTX therapy and thus reducing the MTX-related toxicities. However, further studies with larger data set and well-designed models are required to validate our findings.     

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR)gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis wasto clarify the precise association. A systematic literature search was conducted to identify all relevant studies.Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association.In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria.Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism(TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89,p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated thatMTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85,95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup(TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFRA1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83,p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CCvs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that theMTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.     

The MTHFR C677T polymorphism and prostate cancer risk: new findings from a meta-analysis of 7306 cases and 8062 controls

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P< 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P< 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P< 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.     

Quantitative assessment of the association between MTHFR C677T polymorphism and colorectal cancer risk in East Asians

A great number of studies regarding the association between MTHFR C677T polymorphism and risk of colorectal cancer (CRC) in East Asians were published, but the results were inconsistent. Thus, a meta-analysis was performed to investigate the association. PubMed, Embase, and CBM databases were searched for eligible publications. Pooled odds ratios (ORs) with 95?% confidence intervals (95?% CIs) were calculated using random or fixed effect models. Finally, 24 case?Ccontrol studies with a total of 7,230 CRC cases and 9,285 controls were included. Meta-analyses of a total of 24 studies showed there was a statistically significant association between MTHFR C677T polymorphism and decreased CRC risk in East Asians under four genetic models (T versus C, OR?=?0.92, 95?% CI 0.85?C0.99; TT versus CC, OR?=?0.80, 95?% CI 0.69?C0.94; TT versus CT/CC, OR?=?0.82, 95?% CI 0.71?C0.95; TT/CT versus CC, OR?=?0.92, 95?% CI 0.86?C0.98). The cumulative meta-analyses for the allele contrast (T versus C), homozygote (TT versus CC), dominant (TT/CT versus CC), and recessive (TT versus CT/CC) models all showed a trend of more obvious association as information accumulated by year. Subgroup analyses by country further identified this association in Korea and Japan. This meta-analysis suggests that MTHFR C677T polymorphism is associated with decreased risk of colorectal cancer in East Asians, and MTHFR 677T variant has a protective effect on colorectal cancer.     

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Objective: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to prolinetoserineamino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individuallypublished studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize thepossible association. Methods: A systematic literature search up to August 27, 2012 was carried out in PubMed,EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs)with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs.C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixedorrandom-effect models. Results: We identified 12 case-control studies including 3,041 cases and 3,128 controlsfor the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and riskof bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, inthe subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95%CI = 1.08–1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95%CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. Conclusions: The results suggest that NQO1rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.     

MTHFR C677T Polymorphism and Ovarian Cancer Risk: A Meta-analysis

Background: Many studies have investigated possible association between the methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism and ovarian cancer risk, but the impact is still unclear owing tothe obvious inconsistencies. This study was performed to quantify the strength of the association with a metaanalysis.Methods: We searched the PubMed, Embase, and CNKI databases for studies relating the associationbetween MTHFR C677T polymorphism and ovarian cancer risk and estimated summary odds ratios (ORs) withconfidence intervals (CIs) for assessment. Results: Finally, eight studies with a total of 3,379 ovarian cancer casesand 4,078 controls were included into this meta-analysis. Overall the showed that MTHFR C677T polymorphismwas not associated with ovarian cancer risk under all genetic models (ORT versus C = 1.03, 95%CI 0.90-1.18; ORTTversus CC = 1.08, 95%CI 0.79-1.47; ORTT versus TC+CC = 1.05, 95%CI 0.80-1.37; ORTT +TC versus CC = 1.05, 95%CI 0.86-1.21).Meta-analyses of studies with confirmation of HWE also showed no significant association. Subgroup analyses byethnicity showed there was no significant association in the Caucasians but MTHFR C677T polymorphic variantT contributed to increased risk of ovarian cancer in East Asians. No evidence of publication bias was observed.Conclusion: Meta-analyses of available data show that MTHFR C677T polymorphism is not associated withovarian cancer risk in Caucasians, but the MTHFR polymorphic variant T may contribute to increased risk inEast Asians.     

Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNAfunction. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number ofhuman diseases, including cancer. Objective: The association between MTHFR C677T and A1298C genotype andhaplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials andMethods: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89controls taken from the general population, employing the PCR-RFLP technique. Results: The frequency of thegenotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphismat this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3%among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likelyto have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CCgenotype were 9.9 and 6.7 times more likely to have LC, respectively (ORsmokers=9.9; 95%CI: 1.2-84.5, p=0.018;ORmen=6.6; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showeddifferential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotypewas associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). Conclusions: Thegenetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele atposition 677) may modulate the risk for LC development among the Jordanian population. Risk associated withthe 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folatemetabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.     

MTHFR polymorphisms and pancreatic cancer risk: lack of evidence from a meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported tobe associated with pancreatic cancer, but the published studies had yielded inconsistent results.We thereforeperformed the present meta-analysis. Methods: A search of Google scholar, PubMed, Cochrane Library andCNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms withpancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publicationbias were also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C)were involved in this meta-analysis. Overall, C667T(TT vs. CC : OR = 1.61, 95%CI = 0.78 - 3.34; TT vs. CT :OR = 1.41, 95%CI = 0.88-2.25; dominant model: OR = 0.68, 95%CI = 0.40-1.17; recessive model: OR = 0.82,95%CI = 0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14;dominant model: OR=1.01, 95%CI = 0.47-2.20; recessive model: OR = 1.01, 95%CI = 0.80-1.26) did not increasepancreatic cancer risk. Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T andA1298C) were not associated with pancreatic cancer risk.     

MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to beassociated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessedthe relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysisapproach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized.The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was alsocalculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included inthis meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25;Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CCvs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01,95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk.Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associatedwith pancreatic cancer risk.     

MTHFR gene polymorphisms and bladder cancer susceptibility: a meta-analysis including race, smoking status and tumour stage

Epidemiological studies have investigated that functional polymorphisms in the methylene-tetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the numerous published studies have reported inconclusive results. The objective of the current study was to conduct an updated analysis in order to investigate the association between polymorphisms in the MTHFR gene and risk of bladder cancer. We searched the Pubmed database for all articles published up to March 31, 2011 that addressed bladder cancer and polymorphisms and variants or mutations of MTHFR for analysis using statistical software. Results for two polymorphisms (C677T and A1298C) in 27 case-control were studies from 15 articles indicated individuals carrying the 677T allele (TC or TT+TC) to have a reduction to a 29% or 21% compared to the wild genotype (CC) in mixed populations (OR: 0.71, 95%CI: 0.55-0.93 or OR: 0.79, 95%CI: 0.64-0.97, respectively) and it is shown that there is significant positive associations between A1298C polymorphism and bladder cancer in Africans (OR: 1.24, 95%CI: 1.02-1.52 for C vs.A; OR: 1.35, 95%CI: 1.10-1.66 for CA vs. AA; OR: 1.29, 95%CI: 1.08-1.55 for CC+CA vs. AA). However, no significant relationship was found in two polymorphisms in the stratified analysis by smoking status. Interestingly, individuals carrying the 677T allele (TT+TC) demonstrated a higher percentage of invasive than superficial cases (OR: 1.38, 95%CI: 1.13-1.69). The results from the current update analysis suggest that C677T and A1298C polymorphisms in the MTHFR gene are associated with bladder cancer risk and prognosis. Further evaluation based on more studies with larger groups of patients are now required.     

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphismand gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Metpolymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through asearch of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese BiomedicalLiterature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphismand gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of ninecase-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found thatXRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10,95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29,95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was foundin Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20).This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especiallyfor Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scaleand well-designed studies are needed to confirm our results.     

Comment on: “Association Between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: A Meta-Analysis of 5,193 Cases and 6,645 Controls”

Dear editor We read with great interest the recent article by Namazi and colleagues, “association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta-analysis of 5,193 cases and 6,645 controls”(Namazi et al., 2015). There are some important negative points decrease the reliability of the article. Firstly, some contradictory findings exist in this meta-analysis. The author found a significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under the overall dominant and heterozygous model in Caucasian descent. Our review demonstrated inconsistent results in texture (CC+CT vs. TT: OR=0.575, 95%CI=0.498-1.665, P<0.001, Pheterogeneity=0.00, I2=83%) and diagram of overall dominant model (CC+CT vs. TT: OR=0.904, 95%CI=0.796-1.027, P=0.120). On the other hand, in a stratified analysis by ethnicity, the P value of heterozygous model in Caucasian descent is more than 0.05 (CT vs. TT: OR=0.929, 95%CI=0.806-1.070, P=0.308, Pheterogeneity=0.002, I2=57%). Therefore, it seems to exist no significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under mentioned genetic models. Moreover, the author reported that the dominant and allelic genetic models of the XRCC3 Thr241Met polymorphism were significantly correlated with increasing risk of CRC in Asian population (Dominant model: CC+CT vs. TT: OR=0.609, 95%CI=0.411-0.902, P=0.013, Pheterogeneity=0.54, I2=0.00%; Allelic model: C vs. T: OR=0.708, 95%CI=0.605-0.829, P=0.000, Pheterogeneity=0.000, I2=92%). Conversely, the OR of dominant and allelic models in Asian descent represent decreasing CRC risk.     

MTHFR C677T Polymorphism and Pancreatic Cancer Risk:a Meta-analysis

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate,and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Method: Aliterature search was performed using Pubmed and CNKI databases for published studies through May 2012.We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFRC677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a totalof 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysisshowed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancerrisk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41).However, no significant association was found in Caucasians. Conclusion: The MTHFR C677T polymorphismis associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studieswith a larger sample size are needed to further clarify this association.