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.     

XRCC1 polymorphisms and pancreatic cancer: A meta-analysis

Objective:To assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.Methods:We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.Results:Four studies with 1343 cases and 2302 controls were included.Our analysis found:at codon 194,the Trp allele did not decrease pancreatic cancer risk (Arg/Arg versus Trp/Trp:OR=0.97;95% CI:0.48-1.96;P=0.97;Arg/Arg versus Arg/Trp:OR=0.89;95% CI:0.70-1.13;P=0.55;Arg/Trp versus Trp/Trp:OR=1.06;95% CI:0.52-2.16;P=0.90);at codon 280,only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk;at codon 399,the Gln allele also showed no signi?cant effect on pancreatic cancer compared to Arg allele (Arg/Arg versus Gln/Gln:OR=0.94;95% CI:0.74-1.18;Arg/Arg versus Arg/Gln:OR=0.97;95% CI:0.83-1.13;Arg/Gln versus Gln/Gln:OR=0.97;95% CI:0.77-1.22).The shape of the funnel plot and the Egger’s test did not detect any publication bias.Conclusion:There is no evidence that XRCC1 polymorphisms (Arg194Trp,Arg280His,and Arg399Gln) are associated with pancreatic cancer risk.     

MTHFR C677T and colorectal cancer risk: A meta-analysis of 25 populations

The common functional methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the risk of colorectal cancer (CRC), but data from published studies with individually low statistical power are conflicting. To clarify the role of MTHFR C677T genotype in CRC, we considered all available studies in a meta-analysis. Studies reporting on MTHFR C677T genotype and CRC were searched in PubMed up to April 2006. The principle prior hypothesis was that homozygosity for MTHFR 677TT would be associated with reduced risk of CRC. Data were available for 29,931 subjects, including 12,243 with CRC, from 25 independent populations. Compared to the homozygous CC genotype, the MTHFR 677TT genotype was associated with a reduced risk of CRC (odds ratio (OR): 0.83; 95% confidence interval (CI): 0.75-0.93; p = 0.001). There was some heterogeneity among the results of individual studies, but this was not statistically significant (heterogeneity p = 0.12; I2 = 25.8%). Heterozygosity for MTHFR 677 did not influence CRC risk (OR: 0.99; 95% CI: 0.94-1.04). These findings indicate that individuals homozygous for the MTHFR 677TT genotype are at moderately reduced risk of CRC, and support the proposal that common genetic variation in the MTHFR gene contributes to CRC susceptibility, probably accounting for at least 9% of the total incidence.     

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.     

MTHFR C677T polymorphism and colorectal cancer risk in Asians, a meta-analysis of 21 studies

Background: Previous studies concerning the association between methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism and colorectal cancer risk in Asian populations generated conflicting results.A meta-analysis was therefore performed to allow a more reliable estimate of any link. Methods: Relevantstudies concerning the association between the MTHFR C677T polymorphism and risk of colorectal cancer wereincluded into this meta-analysis. The quality of the studies was assessed according to a predefined scale. Oddsratios (ORs) and 95% confidence intervals (CIs) were determined for this gene-disease association using fixedor random effect models according to the heterogeneity between included studies. Results: Finally, 21 studieswith a total of 6692 cases and 8266 controls were included. Meta-analyses showed that there was an obviousassociation of the MTHFR 677T allele with decreased risk of colorectal cancer (OR = 0.91, 95%CI=0.85-0.98,P=0.011). Subgroup analyses by country further identified this association, with dietary folate as the main sourceof heterogeneity. Conclusion: The MTHFR 677T allele is associated with a lower risk of colorectal cancer inAsian populations, and there is effect modification by population plasma folate.     

Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis

Background/Aims: Studies of associations between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer (CRC) in Asian populations have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTT1 polymorphism on the risk of developing colorectal cancer. Methods: A literature search of PubMed and EMBASE up to June 7, 2011 was conducted and 13 eligible papers were finally selected, involving totals of 4,832 CRC cases and 7,045 controls. Subgroup analyses were performed according to the sample size and the research designwith the software programs Review Manager (version 5.0.10) and STATA (version 9.2). Results: Analyses of all relevant studies showed an increased CRC risk was significantly associated with the null genotypes of GSTT1 (OR=1.09, 95%CI=1.01-1.17, POR=0.027; I2=40.2%). Besides, a more obvious association was observed after heterogeneity was eliminated (OR=1.13, 95%CI 1.04-1.23, POR=0.002; I2=0.0%). Subgroup analyses and sensitivity analysis further identified an association in Asians. Conclusions: This meta-analysis demonstrated the GSTT1 null genotype to be associated with an increased risk of CRC in Asian populations.     

Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies

Background

Diabetes mellitus (DM) is widely considered to be associated with risk of pancreatic cancer (PaC), however, whether DM is a cause or a consequence of PaC is still controversial. We examined this association by conducting a detailed meta-analysis of cohort studies.

Methods

Studies were identified by searching Medline and Embase through November 30, 2010. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

A total of thirty-five cohort studies were included in this meta-analysis. DM was associated with an increased risk of PaC (the summary RRs = 1.94; 95% CI, 1.66-2.27), with significant evidence of heterogeneity among these studies (p < 0.001, I² = 93.6%). Subgroup analyses revealed that the increased risk of PaC was independent of geographic locations, sex, study design, alcohol consumption, body mass index (BMI) and smoking status. In addition, the relative risk of PaC was correlated negatively with the duration of DM, with the highest risk of PaC found among patients diagnosed within less than 1 year. There was no significant publication bias (p = 0.136 for Egger’s regression asymmetry test).

Conclusions

Findings from this meta-analysis strongly support that diabetes is associated with an increased risk of PaC in both males and females and that DM is both an early manifestation and an etiologic factor of pancreatic cancer.     

Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis

Epidemiologic evidence suggests a family history of pancreatic cancer (PC) is a risk factor for the disease, yet the magnitude of risk varies between studies. We performed a systematic review of studies that quantified familial risks of PC, and through a meta-analysis, obtained more precise estimates of familial risk. A MEDLINE search identified published studies that reported relative risks (RR) of PC associated with a family history of the disease. A random effects model was used to summarize study-specific RRs and 95% confidence intervals (CI). Sensitivity and sub-group analyzes were performed. Seven case–control and two cohort studies involving 6,568 PC cases were identified. There was no evidence of statistical heterogeneity between studies (I² = 0%; P = 0.483). Results from case–control (RR = 2.82; 95% CI: 1.99–3.66) and cohort (RR = 1.62; 95% CI: 1.28–1.97) studies showed a significant increase in PC risk associated with having an affected relative, with an overall summary RR = 1.80 (95% CI: 1.48–2.12). Similar RR were observed for early (RR = 2.69; 95% CI: 0.56–4.82) and later (RR = 3.41; 95% CI: 0.79–6.03) onset disease in the index case. Data was too sparse to generate an overall summary RR based on the number or type of affected relatives. Individuals with a family history of PC have nearly a two-fold increased risk for developing PC compared to those without such a history. Families with two or more PC cases may benefit from comprehensive risk assessment that involves collection of detailed family history information and data regarding various risk factors for PC, especially smoking history. Those at highest risk may be referred to screening programs and studies; these are important steps toward early detection and greater odds of surviving this disease.     

MTHFR gene polymorphisms in bladder cancer in the Turkish population

Bladder cancer is the 9th most common cancer and is responsible for malignancy related death all on the world. Folate and folate related enzyme polymorphisms related to the cancer risk. The methylene tethrahydrofolate reductase (MTHFR) enzyme is folate related and association of bladder cancer and MTHFR gene. Our purpose was to assess the prevalence of MTHFR gene 677 CT and 1298 AC polymorphisms and Bladder cancer in Turkey. We intended that bladder cancer patients and controls and we used the Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. The MTHFR gene C677T and A1298C polymorphisms were associated with an increased risk of bladder cancer in our population (For the MTHFR gene C677T polymorphism and A1298C polymorphism; p=0.036<0.05; p=0.278>0.05 respectively). Consequently, the MTHFR gene C677T polymorphism augments the risk of bladder cancer in Turkey.     

MTHFR C667T polymorphism association with lung cancer risk in Henan province: a case-control study

The current study was performed to assess any association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of lung cancer in Henan province. This case-control study involved94 patients with newly histological confirmed lung cancer and 78 healthy controls. Genotyping was achieved with peripheral blood lymphocytes DNA and association of the polymorphism with risk of lung cancer was estimated by unconditional logistic regression analysis. The frequencies of the MTHFR 667TT genotype were 37.2% in cases compared with 23.1% in controls (χ2 = 4.008, P = 0.045). Individuals with the 667CC/CT genotype displayed a significantly reduced risk of lung cancer compared with those with the TT genotypes [adjusted odds ratio (OR), 0.506; 95% confidence interval (95% CI), 0.258 - 0.991]. The C667T polymorphism might have a significant effect on the occurrence of lung cancer in Henan province.     

Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis

Inflammation is one of the early phases in the development of gastric cancer. Therefore, several studies have examined the association of polymorphisms in tumour-necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta-analysis reviews and summarises published evidence for these associations. Searching several databases yielded 24 independent studies that reported on the associations between TNF-A polymorphisms and gastric cancer risk. We analysed available data for the most commonly investigated polymorphisms: TNF-A -308G>A (23 studies), TNF-A -238G>A (9 studies), and TNF-A -857C>T (5 studies). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in the random-effects model using the DerSimonian-Laird method. Q-statistic and I(2)-statistic were calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects. The overall ORs (95% CIs) for AG and AA genotypes vs GG genotype for TNF-A -308 were 1.09 (0.94-1.27) and 1.49 (1.11-1.99), respectively. For TNF-A -238, the corresponding ORs (95% CIs) were 1.05 (0.84-1.33) and 1.25 (0.30-5.26), respectively. The overall ORs (95% CIs) for CT and TT genotypes (vs CC) for TNF-A -857 were 1.06 (0.89-1.27) and 1.57 (0.91-2.70), respectively. The statistically significant association between TNF-A -308GG and gastric cancer was limited to western populations. This association showed little heterogeneity (I(2)=0) and remained consistently strong when analyses were limited to anatomic and histologic subtypes of gastric cancer, or limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to larger studies. These same subgroup analyses did not change results associated with other polymorphisms. In conclusion, TNF-A -308AA genotype was associated with a statistically significant increased risk of gastric cancer, whereas other studied polymorphisms were not. The association between TNF-A -857TT genotype and gastric cancer was near significant, and may become significant if more studies are published.     

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.     

MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.     

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.     

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。     

Association between the FAS/FASL polymorphisms and gastric cancer risk: a meta-analysis

Objective: FAS/FASL gene promoter polymorphisms have been repeatedly associated with gastric cancer risk, but findings are inconclusive across studies. To address a more precise estimation of the relationship, a meta-analysis was performed. Methods: Data were collected from the Pubmed, Medline and EMBASE databases, with the last report up to 1 December, 2011. Crude ORs with 95% CIs were used to assess the strength of the association by (1) the additive, (2) the codominant, (3) the dominant, and (4) the recessive models. Results: A total of seven studies, including six studies on FAS -1377G>A polymorphism, five studies on FAS -670A>G polymorphism, and six studies on FASL -844T>C polymorphism, were identified in the current meta-analysis. Overall, an association of FAS -1377G>A (AA versus GG: OR = 1.313, 95% CI = 1.045-1.650, Ph = 0.347, I2 = 10.8) and FASL -844T>C (CC versus TT: OR = 1.352, 95% CI = 1.043-1.752, Ph = 0.461, I2 = 0.0) polymorphisms with gastric cancer was found in the codominant model. However, we did not detect any association between gastric cancer and the FAS -670A>G polymorphism. In the subgroup analysis by ethnicity, similar elevated risks were also observed in Asian population for FAS -1377G>A (AA versus GG: OR = 1.309, 95% CI = 1.041-1.646, Ph = 0.240, I2 = 27.3) and FASL -844T>C (CC versus TT: OR = 1.420, 95% CI = 1.081-1.865, Ph = 0.524, I2 = 0.0) polymorphisms. Conclusions: This meta-analysis indicated that FAS -1377G>A and FASL -844T>C polymorphisms might be associated with gastric cancer risk.     

术中放疗应用于胰腺癌的疗效与安全性meta分析

目的比较术中放疗(IORT)联合常规治疗(手术联合放化疗)与单纯常规治疗对胰腺癌疗效与安全性等预后的影响。方法全面检索PubMed、Cochrane Library、Web of Science、Embase、维普、知网、万方、中国生物医学文献服务系统(SinoMed)等数据库收录的文献, 对符合纳入标准的文献进行筛选并提取数据, 采用RevMan 5.4软件进行meta分析。结果共纳入11项研究, 共813例患者, 根据合并结果显示, 与单纯常规治疗相比, IORT联合常规治疗可提高胰腺癌的总体生存率(HR=0.66, 95%CI为0.54～0.81, Z=4.03, P<0.001), 且不会增加治疗相关不良反应(OR=1.00, 95%CI为0.69～1.46, Z=0.01, P=0.99), 但不能使局部控制率获益(HR=0.56, 95%CI为0.31～1.01, Z=1.93, P=0.05)。结论 IORT联合常规治疗组胰腺癌患者总体生存率明显优于单纯常规治疗组, 两组的不良反应无差异, 值得临床推广应用。     

XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis

Many studies have examined the association between the XRCC3 Thr241Met gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Ultimately, 17 studies, comprising 4123 lung cancer cases and 5597 controls were included. Overall, for T allele carriers (TC + TT) versus the wild-type homozygotes (CC), the pooled OR was 0.95 (95% CI = 0.87-1.04 P = 0.228 for heterogeneity), for TT versus CC the pooled OR was 0.99 (95% CI = 0.86-1.15 P = 0.315 for heterogeneity). In the stratified analysis by ethnicity, histological types of lung cancer and smoking status, no any significantly risks were found for (C/T + T/T) vs C/C or T/T vs C/C. No publication bias was found by using the funnel plot and Egger''s test.Overall, there is no evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk stratified analysis by ethnicity, histology and smoking status.     

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.