Methylenetetrahydrofolate Reductase Genetic Polymorphisms Research Articles

Effects of MTHFR Genetic Polymorphisms on Toxicity and Clinical Response of Irinotecan-Based Chemotherapy in Patients with Colorectal Cancer

This meta-analysis aims to evaluate the effects of common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene on the toxicity and clinical responses of irinotecan-based chemotherapy in patients with colorectal cancer (CRC). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from their inception through November 1st, 2013 without language restrictions. Meta-analysis was conducted with the use of the STATA 12.0 software. Crude odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated. Seven clinical cohort studies with a total of 815 CRC patients met the inclusion criteria. Two common polymorphisms (677 C>T and 1298 A>C) in the MTHFR gene were assessed. The results from our meta-analysis suggested that MTHFR genetic polymorphisms might significantly decrease the rate of grade 3/4 toxicity of irinotecan-based chemotherapy in CRC patients (OR=0.53, 95% CI: 0.32-0.89, p=0.015). Furthermore, we also demonstrated that MTHFR genetic polymorphisms strongly correlated with good clinical responses (complete response+partial response) to irinotecan-based chemotherapy in CRC patients (OR=1.47, 95% CI: 1.05-2.04, p=0.024). Our findings provide empirical evidence that MTHFR genetic polymorphisms may decrease the toxicity of irinotecan-based chemotherapy and increase the clinical benefits for CRC patients. Thus, MTHFR genetic polymorphisms may be screened to predict the clinical responses to irinotecan-based chemotherapy in CRC patients.

Haplotype analysis of the C677T and A1298C polymorphisms of MTHFR and susceptibility to chronic myeloid leukemia

I have read with great interest the recent study by Khorshied et al. [1], which has been published in the Medical Oncology. The authors investigated the possible association between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR; EC: 1.5.1.20; OMIM: 607093) at nucleotides 677 (C677T, rs.1801133) and 1298 (A1298C, rs.1801131) and the risk of chronic myeloid leukemia (CML) in an Egyptian sample. The authors included 97 CML patients and 130 ageand gender-matched healthy controls in their study. They found that there is no significant association between these polymorphisms and the susceptibility to CML. I would like to make a few comments about the study.

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case-control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR) = 1.09, 95 % confidence interval (95% CI) 1.01-1.17; TT versus CC, OR = 1.17, 95% CI 1.00-1.38; TT/CT versus CC, OR = 1.12, 95% CI 1.00-1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR = 0.65, 95% CI 0.46-0.91; CC versus AA/AC, OR = 0.64, 95% CI 0.46-0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.

Genetic Polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) Genes Associated With Pathological Characteristics of Prostate Cancer in the Ecuadorian Population

IntroductionThe methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) enzymes act in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G and MTRR A66G, cause alteration in the homocysteine levels and reduced enzymatic activity that generates deficiency in the assimilation of folates associated with DNA damage; that is, why it is important to know if the single nucleotide polymorphisms are associated with the pathological characteristics and development of prostate cancer, through a case-control retrospective study. MethodsDNA was extracted from 110 healthy and 104 affected men. The genotypes were determined by means of the polymerase chain reaction-restriction fragment length polymorphism and confirmed with genomic sequencing. ResultsWe found significant association between the genotypes of the MTHFR C677T polymorphism: C/T (odds ratio [OR]=2.2; 95% confidence interval [CI]=1.3–3.9; P=0.008) and C/T+T/T (OR=2.2; 95% CI=1.3–3.9; P=0.009) with the risk of prostate cancer development, and a slight association with MTRR A66G. Regarding pathological characteristics, we found significant risk between the C/T+T/T genotypes and the Gleason score (7–10) of poorly differentiated carcinoma (OR=5.2; 95% CI=1.7–16.2; P=0.007). On the other hand, a significant association between A1298C, A66G, and A2756G with the pathological characteristics was not found (P>0.05). ConclusionsThe MTHFR C677T polymorphism has significant effects on susceptibility to prostate cancer in Ecuadorian population, especially with the Gleason grade.

5,10‐Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms: genotype frequency and association with homocysteine and folate levels in middle‐southern Italian adults.

Two genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) can influence the plasma homocysteine (Hcy) levels, especially in the presence of an inadequate folate status. The aim of this study was to evaluate the frequencies of C677T and of A1298C MTHFR polymorphisms and their correlation with Hcy and serum folate concentrations in a population of blood donors living in a region of middle-southern Italy (the Molise Region). One hundred ninety seven blood donors were studied for total plasma Hcy, serum folate and C677T and A1298C MTHFR genotypes. The frequency of C677T genotypes was 20.8% (CC), 49.8% (CT) and 29.4% (TT); for the A1298C genotypes: 48.7% (AA), 43.7% (AC) and 7.6% (CC). Hcy and serum folate concentrations were significantly different among genotypes of the C677T polymorphism (CC versus CT versus TT: <0.0001 both for Hcy and folate), with Hcy values increasing, and serum folate decreasing, from CC to TT subjects. Regarding to A1298C polymorphism, the difference among genotypes (AA versus AC versus CC; p: 0.026 for Hcy and 0.014 for serum folate), showed an opposite trend for both parameters, with Hcy higher in the wild-type and lower in the homozygotes and serum folate higher in CC than in AA subjects. In conclusion, we found a high frequency of MTHFR allele associated with high level of Hcy and low levels of folate in an Italian southern population.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val and susceptibility to ovary cancer: a systematic review and meta-analysis

Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR = 0.980, 95% CI = 0.756-1.270, P h = 0.088, P = 0.877; dominant model: OR = 1.022, 95% CI = 0.864-1.208, P h = 0.033, P = 0.803; recessive model: OR = 1.050, 95% CI = 0.803-1.373, P h = 0.032, P = 0.723; allele comparison model: OR = 1.028, 95% CI = 0.898-1.178, P h = 0.012, P = 0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.

Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Colorectal Cancer among Jordanian Population

Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA synthesis and repair. We here aimed to investigate two common polymorphisms, C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer (CRC) cases among Jordanian. 131 CRC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of MTHFR C677T among Jordanians to be CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3% among controls. Carriers of the TT genotype were less likely to have CRC (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype. Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant association between genetic polymorphism at this site and CRC. Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the TA haplotype (677T-1298A) between cases and controls. The TA haplotype was associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9, p=0.03). The genetic polymorphism of MTHFR at 677 and the TA haplotype may modulate the risk for CRC development among the Jordanian population. Our findings may reflect an importance of genes involved in folate metabolism in cancer risk.

Association of Methylenetetrahydrofolate reductase genetic polymorphisms and folate intake with susceptibility of esophageal squamous cell carcinoma: A meta-analysis

Objectives: We conducted an update meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk.Methodology: PubMed, EMBASE and the CNKI were searched in our study. The pooled Odds ratio (ORs) and 95% confidence intervals (CIs) of MTHFR C677T and folate intake and ESCC risk from each study were pooled using meta-analysis.Results: Twenty studies (4271 cases and 5559 controls) were included for meta-analysis. MTHFR 677 CT and TT genotypes were associated with an increased risk of ESCC, with OR(95%CI) of 1.48(1.25-1.77) and 1.65(1.24-2.20). By subgroup analysis, we found individuals carrying CT+TT genotype and low intake of folate had an increased risk of ESCC risk when compared with CC genotype [OR(95CI%)=1.55(1.02-2.57)]. There was a significant interaction between folate intake and ESCC. No publication bias was found among studies regarding MTHFR 677 CT and TT by Egger’s test.Conclusions: Our meta-analysis indicated MTHFR 677CT and/or TT genotypes are associated with the risk of ESCC, and folate could modify their association.doi: http://dx.doi.org/10.12669/pjms.292.2928How to cite this:Shujuan Y, Yuanyuan W, Jianxing Z, Xin-yue C. Association of Methylenetetrahydrofolate reductase genetic polymorphisms and folate intake with susceptibility of esophageal squamous cell carcinoma: A meta-analysis. Pak J Med Sci 2013;29(2):693-698. doi: http://dx.doi.org/10.12669/pjms.292.2928This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Methylenetetrahydrofolate Reductase Genetic Polymorphisms and Esophageal Squamous Cell Carcinoma Susceptibility: A Meta-analysis of Case-control Studies

Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

Hyperhomocysteinemia and of Methylenetetrahydrofolate Reductase (C677T) Genetic Polymorphism in Patients with Deep Vein Thrombosis.

Aim:To determine the concentration of total plasma homocysteine (tHcy) as well as different genotypes of methylenetetrahydrofolate reductase MTHFR (C677T) in healthy subjects and patients with deep vein thrombosis (DVT).Material and methods:The investigation comprised a total of 160 subjects divided in two main groups: 80 healthy subjects (control group) and 80 patients with deep vein thrombosis. Concentration of tHcy was determined by spectrophotometric cyclic enzymatic method and mutation of MTHFR (C677T) gene was examined by polymerase chain reaction according to Schneider.Results:The results obtained for plasma tHcy in the control group were 11.62±3.43 μmol/L, while tHcy level was significantly higher in patients with deep vein thrombosis as compared to the control group, 15.19±3.63 μmol/L (р<0.001). The analysis of the results has shown that MTHFR (C677T) genetic polymorphism was responsible for mild to moderate hyperhomocysteinemia in the majority of subjects.Conclusion:The level of tHcy in the examined patients was significantly higher in comparison with the control group. Multiple regression analysis has shown that tHcy level in CT and TT genotypes of MTHFR (C677T) was statistically higher in comparison with CC genotype of MTHFR (C677T) in both, the control group and the DVT patients.

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms in ethnic Han women from Linyi

To explore the distribution of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C and methionine synthase reductase (MTRR) 66A/G among ethnic Han females from Linyi, and to correlate it with serum level of homocysteine (Hcy). A cross-sectional study was carried out. Oral epithelial cell samples were collected from 825 subjects. MTHFR and MTRR gene polymorphisms were determined with a Taqman-Minor Groove Binder (MGB) method. Distribution of gene polymorphisms was analyzed and compared with others regions of China including Weifang, Zhengzhou, Deyang and Hainan. A biochemical assay was also carried out to determine the total Hcy in plasma of 281 subjects. The reductase activity of MTHFR was classified into decreased and stable groups according to genetic polymorphism of MTHFR. Correlation between MTHFR groups and total Hcy level were also explored. (1) The frequencies of MTHFR677CC, CT and TT genotypes of the selected subjects were 16.7%, 48.3% and 35.0%, respectively. The frequencies of MTHFR 1298AA, AC and CC genotypes were 76.0%, 21.6% and 2.4%, respectively. And those of MTRR 66AA, AG and GG genotypes were 54.7%, 39.4% and 5.9%, respectively. For the selected subjects, their frequency of MTHFR 677TT genotype was higher than that of Deyang and Hainan (P< 0.01), whilst the frequency of MTHFR 1298CC genotype was lower than that of Deyang and Hainan (P < 0.01), and the frequency of MTRR 66 GG genotype was lower than that of Hainan (P< 0.01). (2) The Hcy level for those with decreased MTHFR activity was significantly higher than those with stable MTHFR activity (P< 0.05). MTHFR gene 677C/T, 1298A/C and MTRR 66A/G polymorphisms in ethnic Han women from Linyi have differed significantly from other regions of China. Decreased MTHFR activity caused by genetic polymorphisms is a risk factor for raised Hcy level.

Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

BackgroundRecurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL. MethodsA meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast. Result(s)MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32–2.13; P<0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04–1.76; P=0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13–1.58; P<0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P=0.0004) and 1.53 for T versus total alleles (P<0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P<0.0001) and 1.80 for T versus total alleles (P<0.027)), but not in Caucasian subgroup. MTHFR A1298CThe study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71–2.67; P=0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98–1.38; P=0.0833) for CC+AC versus total genotypes and 1.04 (95%CI, 0.84–1.29; P=0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found. ConclusionsThese results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.

Erratum to: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) polymorphisms with osteoporotic vertebral compression fracture (OVCF) in postmenopausal Korean women

Hyperhomocysteinemia is associated with the risk of skeletal health problems, such as osteoporosis, low body mineral density, and fracture. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are involved in homocysteine metabolism. We hypothesized that certain genetic polymorphisms of MTHFR and TS that cause altered enzyme activity may lead to hyperhomocysteinemia and affect bone metabolism. Therefore, we determined whether MTHFR 677C>T, MTHFR 1298A>C, TS enhancer region (TSER), and TS 3′-UTR 6 bp insertion/deletion polymorphisms are associated with osteoporotic vertebral compression fracture (OVCF) in postmenopausal Korean women. A total of 308 postmenopausal Korean women were enrolled as study subjects. Among them, 84 were patients with OVCF and 224 were controls. The polymorphisms were analysed by PCR-RFLP methods. Single mutations of MTHFR or TS were not associated with the occurrence of OVCF. However, the combined genotypes 2R3R+2R2R/0bp6bp+6bp6bp (TSER/TS 3′-UTR) and AC+CC/0bp6bp+6bp6bp (MTHFR 1298A>C/TS 3′-UTR) were associated with decreased risk for OVCF. 2R-0bp and 2R-6bp haplotype frequencies of TS were significantly different between the cases and controls. In the present study, the combined genotype of TSER/TS 3′-UTR and MTHFR 1298A>C/TS 3′-UTR was associated with a decreased risk for OVCF in postmenopausal Korean women. However, due to the several limitations of our study including the moderately small sample size, our findings should be considered with caution and further research is needed to draw more definitive conclusions.

Association between parental MTHFR gene polymorphism 677C/T and nonsyndromic cleft lip and palate in offspring

To explore the association between parental genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) 677C/T and occurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring in Shandong Province. MTHFR genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Parents of 89 NSCL/P patients treated at Qilu Hospital from August, 2006 to August, 2008 and those of 64 healthy children were recruited in this case-control study. Frequencies of T and C alleles in mothers of patients and healthy children were 65.73% and 46.09%, and 34.27% and 53.91%, respectively (Chi-square=13.663, P<0.01). Offspring whose mothers had T alleles were 2.243 times more likely to develop NSCL/P (95%CI: 1.408-3.572). Frequencies of T and C alleles in fathers of patients and healthy children were 62.92% and 55.47%, and 37.08% and 44.53%, respectively (Chi-square=2.222, P>0.05). The chance for parents of the patient and control groups to bear an affected fetus carrying homozygous mutations were 43% and 29%, respectively (P>0.05). In Shandong Province, maternal genotype for the MTHFR 677C/T polymorphism has a significant impact on the occurrence of NSCL/P in their offspring, whilst paternal genotype for this polymorphism may not be a risk factor for NSCL/P in their offspring.

MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients

Genetic variations have been proposed to play a role in the susceptibility to diabetic nephropathy. To check for the association of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with the development of diabetic nephropathy among type 2 diabetic patients. Participants comprised 202 patients with type 2 diabetes, of whom 102 were affected with diabetic nephropathy. Genetic variants corresponding to MTHFR C677T, A1298C and ACE I/D genotypes were determined using the PCR technique coupled with digestion and restriction analysis. Cases with diabetic nephropathy had a significantly higher frequency of the MTHFR 677 TT, 677 CT, ACE DD mutant genotypes compared with diabetic cases without nephropathy. Analysis of the association of studied MTHFR C677T, A1298C and ACE I/D polymorphisms with albuminuria showed that the MTHFR 677 T polymorphism, in the recessive and dominant models, was a risk factor for both micro and macroalbuminuria, while the ACE DD mutant genotype was a risk factor for microalbuminuria and the MTHFR 1298C in the dominant model only was a risk factor for macroalbuminuria. These findings indicate that ACE and MTHFR genetic polymorphisms might be considered as genetic risk factors for diabetic nephropathy among patients with type 2 diabetes.

Meta-analysis on the relationship between genetic polymorphism of methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous cell carcinoma in Chinese population

We aimed to evaluate the association of Methylenetetrahydrofolate reductase C677T polymorphism with ESCC. We searched MEDLINE, EMBASE and the Chinese Biomedical Database. All the articles searched were independently reviewed and selected by 2 evaluators according to the predetermined criteria. A total of 10 case-control studies published between 2001 and 2011 were included. When all the studies were pooled, the crude odds ratio (95% CI) of ESCC forindividuals carrying MTHFR 677 CT and TT genotype were 1.70 (1.32 to 2.20) and 2.10 (1.58 to 2.79), respectively. An Egger’s test provided that the effect estimates were not related to study size (p values for MTHFR 677 CT and TT were 0.16 and 0.17, respectively). The meta-analysis provides evidence that MTHFR 677CT/TTplays a carcinogenic role in ESCC, and its effect is modified by alcohol, tobacco and ethnicity. Key words: Methylenetetrahydrofolate reductase C677T, polymorphism, esophageal cancer, meta-analysis.

Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

MP-07.01 Relationship Between Genetic Polymorphisms of Methylenetetrahydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility

In recent years, interest has increased in the role of homocysteine and folate, as modulators of fertility status. The human methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folate metabolism. Data regarding the influence of MTHFR gene polymorphisms on male fertility status are scarce and conflicting. We determined associations between three MTHFR gene polymorphisms (C677T, A1298C, and G1793A), serum folate and total homocysteine (tHcy) levels, with male fertility status and semen parameters.

Genetic Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) and Coronary Artery Disease.

A high plasma homocysteine concentration is a risk factor for atherosclerotic disease and venous thrombosis. Homocysteine levels are influenced by folic acid, vitamin B 6 and vitamin B 12, as well as by hereditary factors. A common genetic variant of the methylenetetrahydrofolate reductase (MTHFR) gene CC 677 T) is associated with thermolability of the MTHFR enzyme and elevated plasma homocysteine concentration, especially in those with low folic acid concentration. The prevalence of point mutation (nucleotide 677 C --> T) in MTHFR was measured in patients with coronary artery disease (CAD) who all underwent coronary artery bypass surgery (62 cases; age 64.0 +/- 9.5 years), and was compared with, age-matched control subjects. In patients with coronary artery disease (CAD), we investigated the prevalence of point mutation (nucleotide 677 C --> T) in MTHFR in comparison with control subjects. Heterozygous (C/T) prevalence for the 677 C --> T mutation in the MTHFR was higher in patients with CAD than in control subjects (P < 0.05). The prevalence of homozygosity (C/C) for wild-type MTHFR was lower in patients with CAD in comparison with control subjects (P < 0.05).

Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer