• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2199-2206
• /
• 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.

• Clinical and Experimental Reproductive Medicine
• /
• 제29권3호
• /
• pp.215-222
• /
• 2002

Objective : Previous studies have suggested that hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR C677T) mutations are associated with increased risk of recurrent spontaneous abortion (RSA). Recently, a second site polymorphism in MTHFR, 1298A-->C, which changes a glutamic acid into an alanine residue, was shown to be associated with a decreased enzyme activity. We tested whether the variant alleles of MTHFR C677T and A1298C are risk factor (biomarker) for RSA. Materials and Methods: We analyzed DNA from a case-control study in the Korean DNA was extracted from blood samples of 118 patients with RSA and 123 healthy fertile patients as the controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results: We found no evidence for an association between 677TT genotype and risk of RSA (OR=1.95, 95% CI=$0.84{\sim}4.50$, p=0.12). However, the MTHFR 1298AC (OR=0.36, 95% CI=$0.20{\sim}0.63$, p=0.0004) and 1298AC+CC (OR=0.35, 95% CI=$0.20{\sim}0.61$, p=0.0002) genotypes were lower among 118 RSA cases compared with 123 controls, conferring a 2.8-fold decrease in risk of RSA, respectively. Moreover, the combined genotypes of MTHFR 677CC/1298AC (OR=0.30, 95% CI=$0.10{\sim}0.88$, p=0.029) and 677CT/1298AC (OR=0.77, 95% CI=$0.60{\sim}0.99$, p=0.043) also showed significantly lower risk than those with MTHFR 677CC/1298AA type. Conclusion: MTHFR 1298AC, MTHFR 677CC/1298AC and 677CT/1298AC genotypes may represent genetic markers for the protection of RSA at least in Korean women.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권18호
• /
• pp.7731-7735
• /
• 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.

• 생물정신의학
• /
• 제12권2호
• /
• pp.114-122
• /
• 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.

• Clinical and Experimental Reproductive Medicine
• /
• 제33권1호
• /
• pp.61-61
• /
• 2006

목 적: 본 연구는 methylenetetrahydrofolate reductase (MTHFR C677T와 A1298C) 유전자 돌연변이형이 자연유산아 발생의 원인 유전자로 작용하는지에 대해 알아보고자 시도하였다. 연구방법: 95명의 자연유산아 조직과 대조군으로 100명의 정상 소아의 혈액 그리고 449명의 정상 성인의 혈액을 채취하여 DNA를 분리하여 사용하였다. 유전자형은 분리된 DNA를 이용하여 중합효소 연쇄반응과 제한효소 절편다형 분석방법으로 결정하였다. 결 과: 자연유산아 그룹은 소아대조군에서 보다 MTHFR 677CC 형 (p=0.014)은 높게, 677CT형 (p=0.063)은 낮게 나타났다. 성인대조군과의 비교에서도 MTHFR 677CT 형의 빈도는 현저히 낮게 나타났다 (p=0.032). 그리고 MTHFR 677CC/1298AC 조합형 유전자의 경우 소아대조군 (p=0.034)과의 비교에서는 현저히 높은 빈도를 나타냈으나, 성인대조군 (p=0.063)과의 비교에서는 높은 경향성은 있었으나 통계학적으로 유의한 차이는 없었다. 결 론: MTHFR 677CC와 MTHFR 677CC/1298AC 유전자형은 자연유산아 발생의 위험인자일 가능성이 높으며, 지속적인 연구가 요구된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.2903-2908
• /
• 2013

Background: Various oncogenes related to cancer have been extensively studied and several polymorphisms have been found to be associated with breast cancer. The current report outlines analysis of germ-line polymorphisms for C677T, A1298C (MTHFR), Leiden, R2 (FV) and 5G/4G (PAI-1) in Turkish breast cancer patients. We studied 51 cases diagnosed with invasive ductal and operable with lymph node-positive breast cancer and 106 women as a control group. Materials and Methods: Peripheric blood-DNA samples were used for genotyping by StripAssay technique which is based on the reverse-hybridization principle and real-time PCR methods and results were compared statistically. Results: The frequency of the MTHFR gene 677T and 1298A alleles were significantly higher in cancer patients than in the healthy subjects. The T allele frequency in codon 677 was 2.3-fold and C allele frequency was 3.1-fold increased in BC when compared to the control group for the MTHFR gene. Both differences were statistically significant (OR: 2.295, CI: 1.283-4.106), p<0.006 and (OR: 3.131, CI:1.826-5.369), p<0.0001 respectively. The R2 allele frequency of FV gene was 5.1-fold increased in the current BC when compared to the control group and that difference was also statistically significant (OR: 5.133, CI: 1.299-20.28), p<0.02. Conclusions: The present data suggest that germ-line polymorphisms of C677T, C1298A for MTHFR and R2 for FV are associated in breast cancer and may be additional prognostic markers related to breast cancer survival. The results now need to be confirmed in a larger group of patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1599-1603
• /
• 2012

Objectives: Since methylenetetrahydrofolate reductase (MTHFR) maintains the balance of circulating folate and methionine and blocks the formation of homocysteine, its regulation in relation to different cancers has extensively been studied in different populations. However, information on Pakistani breast cancer patients is lacking. The MTHFR gene has two most common mutations that are single nucleotide additions which result in change of amino acids C677T to Ala222val and A1298C to Glu429Ala. Methodology: 110 sporadic breast patients with no prior family history of cancer or any other type of genetic disorders along with 110 normal individuals were screened for mutations in exons 1 to exon 9 using single strand conformational polymorphism, RFLP and sequencing analyzer. Results: The p values for the 677CC, 677CT, and 677TT genotypes were 0.223, 0.006, and 0.077, respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 0.555, 0.009, and 0.003, respectively. Conclusions: We found an overall a significant, weak inverse association between breast cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR polymorphism might be population specific in sporadic breast cancer affected patients but many other factors need to be excluded before making final conclusions including folate intake, population and disease heterogeneity.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.3163-3168
• /
• 2013

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권8호
• /
• pp.3101-3109
• /
• 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.

• Nutritional Sciences
• /
• 제9권1호
• /
• pp.35-41
• /
• 2006

It should be concerned to the women with mutated genotype of methylenetetrahydrofolate reductase (MTHFR), C677T or A1298C, since they need more folate than those with wild genotypes. In this study, we evaluated the folate status of Korean women of childbearing age according to their MTHFR polymorpiysm. Dietary folate intakes, plasma and erythrocyte folate concentrations, plasma homocysteine concentrations, and urinary excretions of para-aminobenzoylglutamate (pABG) and para-acetoamidobenzoylglutamate (ApABG) of twenty-five subjects aged between 19 and 35 years old were determined Folate intakes seemed to be inadequate, being only three-quarters of the Korean RDA of folate. More than one-quarter of the subjects was exposed to folate deficiency risk as determined by erythrocyte folate concentration and almost one-quarter of the subjects showed hyperhomocysteinemia, although they had normal plasma folate concentrations. Urinary excretions of pABG and ApABG seemed to be low and ApABG constituted more than $85\%$ of total folate catabolites. There were no significant differences in dietary folate intakes, plasma concentrations of folate and homocysteine, and urinary excretions of pABG and ApABG among the geneotypes of both C677T and A1298C. However, the subjects with 1298AC genotype had significantly lower erythrocyte folate concentration than those with 1298AA. Erythrocyte folate concentration showed an inverse relationship with plasma homocysteine concentration and positive relationships with urinary excretions of pABG and ApABG. The results of this study imply that mutations of 677C$\rightarrow$T and 1298A$\rightarrow$C in the study were not associated with decreased plasma folate and raised plasma homocysteine concentrations. A1298C polymorphism night be, however, more influential on erythrocyte folate concentration than C677T polymorphism, and urinary excretions of folate catabolites, pABG and ApABG, might be reliable indexes of folate nutritional status like plasma homocysteine concentrations.