• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3943-3947
• /
• 2012

Objective: Findings for associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and head and neck cancer risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Methods: Ten published case-control studies were collected and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR A1298C polymorphism and head and neck cancer risk. Sensitivity analysis and publication bias assessment also were performed to guarantee the statistical power. Results: Overall, no significant association between MTHFR A1298C polymorphism and head and neck cancer risk was found in this meta-analysis (C vs. A: OR=1.04, 95%CI=0.87-1.25, P=0.668, Pheterogeneity<0.001; CC vs. AA: OR=1.07, 95%CI=0.70-1.65, P=0.748, $P_{heterogeneity}<0.001$; AC vs. AA: OR=1.06, 95%CI=0.88-1.27, P=0.565, $P_{heterogeneity}<0.001$; CC+AC vs. AA: OR=1.06, 95%CI=0.86-1.30, P=0.571, $P_{heterogeneity}<0.001$; CC vs. AA+AC: OR=1.02, 95%CI=0.69-1.52, P=0.910, $P_{heterogeneity}<0.001$). Similar results were also been found in succeeding analysis of HWE and stratified analysis of ethnicity. Conclusion: In conclusion, our meta-analysis demonstrates that MTHFR A1298C polymorphism may not be a risk factor for developing head and neck cancer.

• Clinical and Experimental Reproductive Medicine
• /
• 제44권3호
• /
• pp.152-158
• /
• 2017

Objective: To identify the associations between polymorphisms of the 3'-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. Methods: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C > A, 4869C > G, 5488C > T, and 6685T > C 3'-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. Results: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178-0.994; p= 0.048) for RPL. Analysis of variance revealed that MTHFR 4869C > G was associated with altered $CD56^+$ natural killer cell percentages (CC, $17.91%{\pm}8.04%$; CG, $12.67%{\pm}4.64%$; p= 0.024) and folate levels (CC, $12.01{\pm}7.18mg/mL$; CG, $22.15{\pm}26.25mg/mL$; p= 0.006). Conclusion: Variants in the 3'-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권18호
• /
• pp.8093-8100
• /
• 2016

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1203-1208
• /
• 2012

Background: Previous studies concerning the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer risk in Asian populations generated conflicting results. A meta-analysis was therefore performed to allow a more reliable estimate of any link. Methods: Relevant studies concerning the association between the MTHFR C677T polymorphism and risk of colorectal cancer were included into this meta-analysis. The quality of the studies was assessed according to a predefined scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for this gene-disease association using fixed or random effect models according to the heterogeneity between included studies. Results: Finally, 21 studies with a total of 6692 cases and 8266 controls were included. Meta-analyses showed that there was an obvious association of the MTHFR 677T allele with decreased risk of colorectal cancer (OR = 0.91, 95%CI=0.85-0.98, P=0.011). Subgroup analyses by country further identified this association, with dietary folate as the main source of heterogeneity. Conclusion: The MTHFR 677T allele is associated with a lower risk of colorectal cancer in Asian populations, and there is effect modification by population plasma folate.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1553-1556
• /
• 2012

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

• Journal of Animal Science and Technology
• /
• 제54권3호
• /
• pp.157-163
• /
• 2012

The male reproduction is precisely controlled by a number of intrinsic and extrinsic factors. These factors usually involve in expressional regulation of various molecules influencing on sperm production in the testis. A number of ways are employed to control the transcription of specific genes, including epigenetic modifications of DNA and histone molecules. DNA methylation of CpG dinucleotides is a commonly used regulatory mechanism for testicular genes associated with the fertility. Previous studies have demonstrated the infertility induced by improper DNA methylation of these genes. In the present research, we attempted to determine transcriptional expression of some of these genes in the rat testis at different postnatal ages using real-time PCR analysis. These genes include neurotrophin 3 (Ntf3), insulin-like growth factor II (Igf2), JmjC-domain-containing histone demethylase 2A 1 (Jhm2da), paired box 8 transcription factor (Pax8), small nuclear ribonucleoprotein polypeptide N (Snrpn), and 5,10-methylenetetrahydrofolate reductase (Mthfr). The expression levels of Ntf3, Igf2, and Snrpn genes were the highest at the neonatal age, followed by transient decreases at the prepubertal age. Expression of Jhm2da and Mthfr genes were continuously increased from the neonate to 1 year of age. The levels of Pax8 mRNA at the early ages were higher than those at the later ages of postnatal development. These findings suggest that expression of some fertility-associated testicular genes in the rat during postnatal period could be differentially regulated by the control of the degree of DNA methylation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권6호
• /
• pp.2597-2604
• /
• 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.