• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5189-5192
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• 2013

Aim: We aimed to investigate the associations of dietary intake of folate, vitamin $B_6$ and $B_{12}$ and MTHFR genotype with breast cancer in a Chinese population. Methods: A matched case-control study was conducted, and 435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. The folate intake, vitamin $B_6$ and vitamin $B_{12}$ were calculated, and MTHFR C665T, C677T and A1298C were analyzed by PCR-RFLP. Results: We found vitamin $B_{12}$ was likely to reduce the risk of breast cancer, and MTHFR 665TT was associated with increased risk of breast cancer. Folate intake, vitamin $B_{12}$ intake and variants of MTHFR C677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patients with low intake of vitamin $B_6$ and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95% CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin $B_6$ and MTHFR 665TT genotype (OR=1.58, 95% CI=1.03-2.49, P=0.03). Conclusion: Our study indicated that the MTHFR C665T polymorphism and vitamin $B_6$ are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer.

• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.114-122
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• 2005

Objectives:Recently in schizophrenia high incidence of MTHFR(methylenetetrahydrofolate reductase), which is a main relating enzyme that reduce homocysteine level, genetic variations were reported. So we examined serum homocysteine level and MTHFR gene polymorphism in Korean schizophrenics. Method:We compared serum homocysteine level and MTHFR polymorphism between 235 schizophrenics (100male, 135female) and 235 normal controls(100male, 135female). C677T and A1298C polymorphism of MTHFR gene were analyzed. Results:1) C677T genetic mutation(CT and TT) were more frequent in schizophrenia group than normal control group(p<0.01). But the difference of A1298C mutation frequency was not found between two groups. 2) In schizophrenia patients, TT genotype of C677T mutation showed significantly higher homocysteine level (29.99uM/L) than other group(CT:13.34uM/L, CC:9.34uM/L p<0.01). 3) MTHFR 677 TT homogeneous mutation genotype showed two times more risk(odds ratio=2.15) than 677CC normal genotype in schizophrenia. Conclusion:Some schizophrenia patients with high homocysteine serum level may have C677T TT genotype. In that case, folate ingestion could be a good management for clinical improvement.

• Korean Journal of Clinical Oncology
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• v.9 no.2
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• pp.80-86
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• 2013

Purpose: Hypermethylation of human mut L homologue 1 (hMLH1) promoter region is known to cause sporadic microsatellite instability (MSI) colorectal cancers. 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in folate metabolism, acting as a methyl donor for DNA methylation. In this study, we investigate whether the polymorphism of MTHFR 677C>T plays a role in the alteration of the promoter-specific hypermethylation, predisposing to MSI colorectal cancers. Methods: Total of 487 sporadic colorectal cancer patients in CHA Bundang Medical Center were collected. MSI was identified when two or more are positive among five microsatellite markers (BAT25, BAT26, D17S250, D5S346, D2S123). The others were classified as microsatellite stable (MSS). Polymorphism of MTHFR 677C>T was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: MSI was observed in 65 of 487 patients (12.73%). MSI colorectal cancers showed similar clinicopathological features with previously reported; younger age onset, right-sided preponderance, mucinous and poorly differentiated histology, lower stage, fewer lymph node metastases than MSS tumors (each P<0.05). The frequency of MTHFR 677TT genotype was 17.7% in the MSI group higher than 14.6% in the MSS group (P=0.17). Although not statistically significant, compared to the MTHFR 677CC referent, MTHFR 677 CT+TT genotype was more likely to have MSI than MSS (odds ratio, 1.81; 95% confidence interval, 0.94 to 3.68; P=0.06). Conclusion: This study demonstrated higher frequency of MTHFR 677TT genotype in MSI colorectal cancers. Furthermore, individuals with MTHFR 677CT+TT variant type might potentially develop MSI rather than MSS colorectal cancers.

• The Journal of Internal Korean Medicine
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• v.23 no.1
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• pp.1-4
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• 2002

Objective : Hyperhomocysteinemia has been proven to be an independent risk factor for stroke. The genetic mutation of methylenetetrahydrofolate reductase(MTHFR) elevates serum homocysteine level, but it still remains controversial whether the MTHFR gene mutation could be a predictor of ischemic stroke. Therefore, we studied if this genetic defect could cause ischemic stroke independently. Methods : We gathered ischemic stroke subjects and age, sex-matched controls. Age, gender, past medical history, smoking habit, serum homocysteine level, and the MTHFR genotype were recorded. General characteristics of ischemic stroke subjects were compared to the controls. We classified the stroke according to the related vessels(small and large artery infarction) and single lesion and multiple infraction. Relevant risk of the MTHFR genotype was evaluated in each stroke subtype with multiple logistic regression analysis. Results : When the controls were compared to the whole ischemic stroke, there was no specific difference except some medical histories. However, further analysis based on stroke subtypes showed important results. The small artery infarction group, multiple infraction group had significant odds ratio of the MTHFR TT genotype adjusted for age, gender, medical history and smoking habit. Conclusions : The MTHFR TT genotype is an independent risk factor for certain types of ischemic stroke, small artery infarction and multiple infarction.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3101-3109
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• 2015

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNA function. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number of human diseases, including cancer. Objective: The association between MTHFR C677T and A1298C genotype and haplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials and Methods: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89 controls taken from the general population, employing the PCR-RFLP technique. Results: The frequency of the genotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and 49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphism at 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 likely to have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CC genotype were 9.9 and 6.7 times more likely to have LC, respectively ($OR_{smokers}=9.9$; 95%CI: 1.2-84.5, p=0.018; $OR_{men}=6.6$; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotype was associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). Conclusions: The genetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele at position 677) may modulate the risk for LC development among the Jordanian population. Risk associated with the 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folate metabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.3
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• pp.217-222
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• 2003

Objective: To investigate the association of genetic background between MTHFR C677T genotype and infertile females with polycystic ovarian syndrome. Materials and Methods: We compared 86 infertile females with polycystic ovarian syndrome (PCOS) with 100 healthy fertile females with one or more offspring. Pyrosequencing analysis for MTHFR C677T variation was performed on polymerase chain reaction (PCR) product of study group. To validate pyrosequencing data of C677T variation for randomly selected 50 samples, we compared the pyrosequencing result with the PCR-RFLP (Restriction Fragment Length Polymorphism) result of MTHFR C677T genotype. Results: The prevalence of the C677T mutant homozygous (TT) was significantly lower (p=0.0085) in females with PCOS (8.14%) than in fertile females (21.00%). MTHFR 677 TT genotype had a decreased risk (3.7-fold) of PCOS compared with wild type (MTHFR 677 CC). Conclusion: Our data support a role for MTHFR mutant homozygous (677 TT) genotype in reducing risk in Korean infertile females with Polycystic ovarian syndrome.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.157-163
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• 2002

The role of the kidney in initiating hypertension has been much debated. The SA gene is expressed in the kidney and is association with hypertension in man and in experimental animal models. Also, increased plasma concentrations of homocysteine have been found in patients with coronary artery disease (CAD) and hypertension. The genetic variation of methlene tetrahydrofolate reductase (MTHFR) gene is related to its enzyme activity and to the plasma homocysteine concentration. In view of the effect of SA and MTHFR as risk factor for cardiovascular diseases, we investigated the Pst I RFLP of the SA gene and C667T mutation of the MTHFR gene in the Korean patients with hypertension. There were no significant differences in the allele and genotype frequencies of these polymorphisms between normotensive and hypertensive subjects. Therefore, our results do not support a possible role of these genes on hypertension in Korean population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.299-302
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• 2013

Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above $310{\mu}g$/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7731-7735
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• 2014

Colorectal cancer (CRC) is the third most common cause of death due to cancer in the worldwide and the incidence is also increasing in Turkey. Our present aim was to investigate any association between germ-line methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and CRC risk in Turkey. A total of 86 CRC cases and 212 control individuals of the same ethnicity were included in the current study. Peripheral blood-DNA samples were used for genotyping by StripAssay technique, based on the reverse-hybridization principle and real-time PCR methods. Results were compared in Pearson Chi-square and multiple logistic regression models. The MTHFR 677TT (homozygous) genotype was found in 20.9% and the T allele frequency 4.2-fold increased in CRC when compared with the control group.The second SNP MTHFR 1298CC (homozygous) genotype was found in 14.0% and the C allele frequency 1.4-fold elevated in the CRC group. The current data suggest strong associations between both SNPs of germ-line MTHFR 677 C>T and 1298 A>C genotypes and CRC susceptibility in the Turkish population. Now the results need to be confirmed with a larger sample size.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2199-2206
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• 2012

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.