• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.647-651
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• 2012

Aim: An epidemiological study was conducted based on an esophageal cancer patient's cohort to investigate the association of folate intake and MTHFR C677T polymorphism with the prognosis of esophageal cancer in a Chinese population. Methods: 167 patients aged 37-75 years who had histological confirmed diagnosis of esophageal squamous cell cancer were collected from Jan. 2006 to Jan. 2008. MTHFR genotypes at the C677T site were analyzed by PCR-based RFLP methods, and the folate intake was computed by multiplying the food intake (in grams) and the folate content (per gram) of food in our questionnaire. Results: We found associations between the prognosis of esophageal cancer and smoking status, T and N stages. Individuals carrying the MTHFR 677CT and TT genotypes showed a shorter survival time than with the CC genotype, with adjusted HRs (95% CI) of 1.20 (0.56-2.15) and 2.29 (1.30-4.28), respectively. Similarly, those carrying MTHFR 677T allele had a 1.86-fold risk of death. A higher folate concentration showed a significant decreased risk of death, with an HR (95% CI) of 0.45 (0.18-0.87). Individuals with high folate intake and the MTHFR 677CC genotype showed a significant decreased risk of esophageal cancer (0.43, 0.25-0.89).Conclusion: Our findings supports the hypothesis that high folate intake and active MTHFR C677T polymorphism may exert protective roles in the prognosis of esophageal cancer in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3763-3766
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• 2012

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. Methods: A literature 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 MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; 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. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2025-2029
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• 2012

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar 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 LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TT vs. 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% decreased LC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5853-5860
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• 2014

Background: Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway and several 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 light on any C677T breast cancer association. Materials and Methods: PubMed, Springer Link, Google Scholar and Elsevier databases were searched for case control studies of associations between MTHFR C677T polymorphism and breast cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. A total of 36 studies including 8,040 cases and 10,008 controls were included in the present meta-analysis. Results: Overall, a significantly elevated breast cancer risk was associated with the T allele and TT genotype in homozygote comparison and dominant genetic models when all studies were pooled into the meta-analysis (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 C677T polymorphism and risk of breast cancer in Asian populations.

• Clinical and Experimental Pediatrics
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• v.54 no.8
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• pp.335-339
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• 2011

Purpose: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). Methods: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. Results: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). Conclusion: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.168-173
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• 2011

Objective: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. Methods: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. Results: No differences were found between the two groups' mean plasma homocysteine levels ($7.6{\pm}1.5{\mu}mol$/L vs. $7.1{\pm}2.1{\mu}mol$/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant ($7.7{\pm}1.1{\mu}mol$/L) had higher homocysteine levels than those with the CC and CT variants ($7.4{\pm}1.9{\mu}mol$/L and $7.4{\pm}1.2{\mu}mol$/L) and those with the CT variant ($19.2{\pm}8.1%$) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants ($17.7{\pm}6.6%$ and $17.9{\pm}7.0%$), but the results of both comparisons were statistically insignificant. Conclusion: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.10-15
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• 2005

Purpose: Recently the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, immature vascular disease, neural tube defect, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancer, and particularly gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metaboism, and influences DNA synthesis and DNA methylation. Generally, folate deficiency is associated with gastrointestinal neoplasms. The amino-acid- changing and enzyme-activity-reducing nucleotide polymorphism (766C$\rightarrow$T/ Ala222Val) has been described in the MTHFR polymorphism and leads to low enzyme activity that may reduce the capacity of DNA methylation and possibly uracil mis-incorporation into DNA. These processes may be critical in the oncogenic transformation of human cells, especially in colorectal carcinomas. We investigated the relationship between the MTHFR polymorphism in gastric cancer and the tumor site, the smoking history, and the alcoholic history. Materials and Methods: Ninety-six (96) individuals with gastric cancer and 287 healthy persons were analyzed. Blood sampling was performed, PCR-RFLP was analyzed, and MTHFR polymorphism genotypes of C/C, C/T, and T/T were obtained and analyzed statistically for their correlation. Results: In the gastric cancer group there were 69 ($72\%$) males and 27 ($28\%$) females. There were also 58 cases ($60\%$) involving the gastric lower body, 20 cases ($21\%$) the gastric mid-body, and 18 cases ($19\%$) the gastric upper body. In the control group there were 169 ($59\%$) males and 118 ($41\%$) females. Among the gastric cancer, 56 ($61\%$) smoking patients, 40 ($39\%$) non-smoking patients, 45($47\%$) alcoholic patients, 51 ($53\%$) non-alcoholic patients. In the gastric cancer group, MTHER polymorphisms were C/C in 18 ($19\%$) cases, C/T in 59 ($61\%$) cases, T/T in 19 ($20\%$) cases. In the control group polymorphisms were C/C 116 ($40\%$) cases, C/T 103 ($36\%$) cases, and T/T 68 ($24\%$) cases (P=0.045). In cases of lower gastric body cancer, polymorphisms were C/C in 16 ($24\%$) C/C in 16 ($24\%$) cases and C/T or T/T in 42 ($72\%$) cases. In cases of upper and mid-body cancer, polymorphisms were C/C in 2 ($5\%$) cases and C/T or T/T 36 ($95\%$) cases (P=0.006). In the non-smoking patient group, polymorphisms were C/C in 5 (12%) cases and C/T or T/T in 35 ($88\%$) cases. In the smoking patient group, C/C in 13 ($23\%$) cases and C/T or T/T in 43 ($77\%$) cases (P=0.189). In the non-alcoholic patient group, polymorphisms were C/C in 6 ($12\%$) cases and C/T or T/T in 45 ($88\%$) cases. In the alcoholic patient group, polymorphisms were C/C in 12 ($26\%$) cases and C/T or T/T in 33 ($74\%$) cases (P=0.063) Conclusion: MTHFR polymorphisms are associated with gastric cancer and tumor site, but not with smoking and alcohol drinking.

• 대한예방의학회:학술대회논문집
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• 2002.10a
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• pp.362-363
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8245-8250
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• 2014

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 was to 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 MTHFRC667 was 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 that MTHFR 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 MTHFR A1298C 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 (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.

• Proceedings of the Korean Nutrition Society Conference
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• 2002.05a
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• pp.142-142
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• 2002