• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1345-1349
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• 2014

Although many epidemiologic studies investigated the methylenetetrahydrofolate reductase (MTHFR) polymorphisms and their associations with esophageal cancer, definite conclusions could not be drawn. To clarify the effects of MTHFR polymorphisms on the risk of esophageal cancer, a meta-analysis was here performed in Chinese populations. A total of 16 studies including 3,040 cases and 4,127 controls were involved in this metaanalysis. Overall, significant associations were found between the MTHFR C677T polymorphism and esophageal cancer risk when all studies in Chinese populations were pooled into the meta-analysis (T vs. C, OR = 1.19, 95% CI = 1.06-1.34; TT vs. CC, OR = 1.35, 95% CI = 1.07-1.70; TT+ CT vs. CC, OR = 1.29, 95% CI = 1.08-1.54; TT vs. CC + CT, OR = 1.19, 95% CI = 1.03-1.37). In subgroup analyses stratified by ethnicity and source of controls, the same results were found in Kazakh (TT vs. CC, OR = 1.38, 95% CI = 1.02-1.87; TT + CT vs. CC, OR = 1.50, 95% CI = 1.03-2.18), in not stated populations (T vs. C, OR = 1.24, 95% CI = 1.08-1.42; TT vs. CC, OR = 1.47, 95% CI = 1.10-1.96; TT + CT vs. CC, OR = 1.30, 95% CI = 1.05-1.60; TT vs. CC + CT, OR = 1.32, 95% CI = 1.12-1.56), and in hospital-based studies (T vs. C, OR = 1.34, 95% CI = 1.19-1.51; TT vs. CC, OR = 1.81, 95% CI = 1.37-2.39; TT + CT vs. CC, OR = 1.51, 95% CI = 1.26-1.83; and TT vs. CC + CT, OR = 1.39, 95% CI = 1.13-1.70). In conclusion, this meta-analysis provides evidence that the MTHFR C677T polymorphism contributes to esophageal cancer development in Chinese populations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.569-573
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• 2012

Early diagnosis and better prognosis of ovarian cancer is still a challenge. Besides environmental risk factors, genetic factors have established a role in pathogenesis of ovarian cancer. Methods: A case-control and a prospective study design conducted in 224 ovarian cancer patients and 432 controls in Chinese population. MTHFR C677T genotyping was done by PCR-RFLP. Results: Patients with ovarian cancer is associated with a higher less number of delivery and less frequent oral contraceptive use. When potential confounding factors adjusted logistic regression analysis between cases and controls were performed, significant association was obtained for 677T/T genotype and ovarian cancer (OR=3.13, 95% CI=1.59-5.72). Cox regression survival analysis showed individuals carrying T/T genotype had significantly increased HR for death in ovarian cancer patients (HR=2.86, 95% CI=1.27-7.93). In conclusion, we observed that the MTHFR C677T polymorphism is associated with the susceptibility and survival of ovarian cancer in Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2491-2494
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• 2012

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 (${\chi}^2$ = 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.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.441-445
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• 1999

Objective: To analyze the methylenetetrahydrofolate reductase (MTHFR) mutation in recurrent spontaneous abortion associated with hyperhomocysteinemia. Material and Method: The blood sample of habitual aborter with high fasting homocysteine level was tested by PCR - RFLP method. Results: The patient was found to be a homozygosity for MTHFR gene mutation that was confirmed by the finding which is consistent with the mutation at the nucleotide 677 C to T, corresponding to Ala to Val. Conclusions: Hyperhomocysteinemia due to MTHFR mutation is a cause of recurrent spontaneous abortion. Therefore, the MTHFR mutation should be examined in the workup of recurrent spontaneous abortion showing hyperhomocysteinemia.

• Journal of Sasang Constitutional Medicine
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• v.13 no.2
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• pp.177-181
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• 2001

Sasang Constitutional Medicine is based on the diversity of Human being and medically developed the response variation to diseases and medicines. The diversity is categorized as four from physiology, pathology, symptoms, to therapy. So that is related the difference of individual characteristics in Western Science. Single nucleotide polymorphism is the basic tool to research genetic polymorphisms. We researched the polymorphism site of MTHFR gene on 1p36.3, which is relatively reported the occlusive vascular disease. In the clinical research of brain infarction, the occurrence was different according to constitution. The 677C/T Polymorphism site of MTHFR was not significantly different in constitution group. But this research was the first trial about the single nucleotide polymorphism according to constitution. The more researchs of many genes are necessary to find the characteristics of constitution.

• 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

• 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.

• Environmental Mutagens and Carcinogens
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• v.23 no.1
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• pp.1-6
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• 2003

The purpose of this study was to evaluate whether the MTHFR variants, folate and vitamin $B_{12}$ deficiencies increase the risk of hyperhomocysteinaemia and adverse pregnancy outcome such as short gestational age or reduced birth weight. Healthy pregnant women (n=136; 24-28 gestational weeks; 20-40 years old), who visited Ewha Womans University Hospital for prenatal care, participated in this study. At the time of delivery, trained nurses recorded the pregnancy outcome from medical chart. We determined maternal MTHFR polymorphisms (C to T subsitution at nucleotide 677) and measured serum homocyteine, vitamin $B_{12}$, and folate concentrations. We compared serum homocysteine level by MTHFR genotype, serum folate and serum vitamin B12 levels using ANOVA. To evaluate the association between serum homocysteine level and pregnancy outcome, we compared the gestational age and birth weight by serum homocysteine levels using multiple regression analysis, adjusting for other potential predictors. Mean level of serum homocysteine was highest among pregnant women of the MTHFR variants with low levels of serum folate and vitamin $B_{12}$. Regarding association with birth outcome, we found the relationship between homocysteine levels and increased gestational age (p=0.03) and reduced birth outcome (p>0.05). Our data demonstrates that serum level of folate and vitamin $B_{12}$ among pregnant women affects significantly serum homocysteine levels, and the genetic polymorphism of MTHFR modulates the relationship between them. However, we did not have conclusive evidence of association between high homocysteine level and adverse pregnancy outcome such as preterm or low birth weight.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4017-4023
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• 2012

Background and Aim: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to be associated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors, family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possible interactions with lifestyle factors in Northeast Thailand. Methods: A hospital-based case-control study was conducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls. Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFR C677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s. rectal cancer risk were assessed using logistic regression analysis. Results: Subjects with frequent and occasional constipation had a higher risk ($OR_{adj.}$=14.64; 95%CI=4.28-50.04 and $OR_{adj.}$=2.15; 95%CI=1.14-4.06), along with those who reported ever having hemorrhoids ($OR_{adj.}$=2.82; 95%CI=1.36-5.84) or a family history of cancer ($OR_{adj.}$=1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk ($OR_{adj.}$=1.82; 95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. Conclusions: This study suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having had hemorrhoids, a family history of cancer and pork consumption.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2597-2604
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• 2012

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.