Annals of Coloproctology

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Relationship between Metabolic Syndrome and MTHFR Polymorphism in Colorectal Cancer: Bong Su Kang, Dae Ho Ahn, Nam Keun Kim, Jong Woo Kim; J Korean Soc Coloproctol. 2011;27(2):78-82. Published online April 30, 2011; DOI: https://doi.org/10.3393/jksc.2011.27.2.78

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Purpose

There have been studies on the relations between metabolic syndrome and colorectal cancer or on the relations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and colorectal cancer, but reports on the relationship between metabolic syndrome, MTHFR polymorphism and colorectal cancer all together are rare. The aim of this study is to find the interrelation between metabolic syndrome and MTHFR polymorphism in colorectal cancer.

Methods

This study investigated 255 colorectal cancer patients (cancer group) who underwent surgery in our hospital from March 2003 to December 2008 and compared those patients to 488 healthy patients (control group). The diagnostic criterion for metabolic syndrome was based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), and the MTHFR 677 polymorphism was analyzed.

Results

When colorectal cancer patients and patients in the control group were classified as MTHFR 677 subtypes, there was no difference between the two groups: CC 87 (34.1%), CT 134 (52.6%), and TT 34 (13.3%) for the cancer group and CC 145 (32.4%), CT 238 (53.1%), and TT 65 (14.5%) for the control group. Distributions of MTHFR 677C/T genotype and allele frequencies in the individuals with and without metabolic syndrome in the cancer group showed no differences. Moreover, we could find no differences in distributions of MTHFR 677C/T genotypes in the clinical and the biomedical variables of individuals with and without metabolic syndrome in the cancer group.

Conclusion

Our results show no relation between metabolic syndrome and MTHFR polymorphism in colorectal cancer. However, a further prospective study, based on a precise diagnostic criterion for metabolic syndrome, is needed.

Citations

Citations to this article as recorded by

Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer
Meng Ye, Guojie Xu, Liming Zhang, Zhihui Kong, Zhenhua Qiu
BMC Cancer.2025;[Epub] CrossRef
Unveiling the link: Evaluating MTHFR gene polymorphisms and colorectal cancer risk through meta-analysis
Yu-wei Wang, Ze-yi Huang, Chen-xue Jin, Xiao-hui Shen, Xiao-feng He, Chang-qing Yang, Mohammad Safiqul Islam
PLOS One.2025; 20(7): e0305517. CrossRef
Prognostic significance of three endothelial nitric oxide synthase (eNOS) polymorphisms and metabolic syndrome (MetS) in patients with colorectal cancer
Eun Ju Ko, Eo Jin Kim, Hye Jung Cho, Jisu Oh, Han Sung Park, Chang Soo Ryu, Jung Oh Kim, Hak Hoon Jun, So Young Chong, Jong Woo Kim, Nam Keun Kim
Genes & Genomics.2022; 44(6): 659. CrossRef
Associations of MTRR and TSER polymorphisms related to folate metabolism with susceptibility to metabolic syndrome
Young Ree Kim, Seung-Ho Hong
Genes & Genomics.2019; 41(8): 983. CrossRef
Association of MTHFR C677T gene polymorphism with metabolic syndrome in a Chinese population: a case–control study
Jin Wang, Lijuan Xu, Hongmiao Xia, Ying Li, Shiqi Tang
Journal of International Medical Research.2018; 46(7): 2658. CrossRef
Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis
Lingyan Xu, Zhiqiang Qin, Feng Wang, Shuhui Si, Lele Li, Peinan Lin, Xiao Han, Xiaomin Cai, Haiwei Yang, Yanhong Gu
Bioscience Reports.2017;[Epub] CrossRef
Associations of MTHFR C677T polymorphism with insulin resistance, results of NURSE Study (Nursing Unacquainted Related Stress Etiologies)
Motahareh Kheradmand, Zhila Maghbooli, Sedigheh Salemi, Mahnaz Sanjari
Journal of Diabetes & Metabolic Disorders.2017;[Epub] CrossRef
Association between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and risk of ischemic stroke in North Indian population: A hospital based case–control study
Amit Kumar, Shubham Misra, Anjali Hazarika, Pradeep Kumar, Ram Sagar, Abhishek Pathak, Kamalesh Chakravarty, Kameshwar Prasad
Egyptian Journal of Medical Human Genetics.2016; 17(4): 359. CrossRef
Risk of prostate cancer and thrombosis-related factor polymorphisms
SOMAYEHSADAT GHASEMI, AYDIN TAVAKOLI, MOHAMAD MOGHADAM, MOHAMAD ALI ZARGAR, MARYAM ABBASPOUR, NASIM HATAMNEJADIAN, AHMAD EBRAHIMI
Biomedical Reports.2014; 2(1): 53. CrossRef
The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case–control studies
Min Tang, Shang-Qian Wang, Bian-Jiang Liu, Qiang Cao, Bing-Jie Li, Peng-Chao Li, Yong-Fei Li, Chao Qin, Wei Zhang
Molecular Biology Reports.2014; 41(7): 4659. CrossRef
Associations of MTHFR C677T and MTRR A66G Gene Polymorphisms with Metabolic Syndrome: A Case-Control Study in Northern China
Boyi Yang, Shujun Fan, Xueyuan Zhi, Da Wang, Yongfang Li, Yinuo Wang, Yanxun Wang, Jian Wei, Quanmei Zheng, Guifan Sun
International Journal of Molecular Sciences.2014; 15(12): 21687. CrossRef
Association of MTHFR C677T polymorphisms and colorectal cancer risk in Asians: evidence of 12,255 subjects
X.-P. Guo, Y. Wang, H. Zhao, S.-D. Song, J. Zhou, Y. Han
Clinical and Translational Oncology.2014; 16(7): 623. CrossRef
Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis
MENGMENG ZHAO, XUELIAN LI, CHENGZHONG XING, BAOSEN ZHOU
Biomedical Reports.2013; 1(5): 781. CrossRef
The 677C>T (rs1801133) Polymorphism in the MTHFR Gene Contributes to Colorectal Cancer Risk: A Meta-Analysis Based on 71 Research Studies
Zan Teng, Lei Wang, Shuang Cai, Ping Yu, Jin Wang, Jing Gong, Yunpeng Liu, Rossella Rota
PLoS ONE.2013; 8(2): e55332. CrossRef
MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies
Xuewen Sheng, Yanxi Zhang, Erjiang Zhao, Su Lu, Xiaoli Zheng, Hong Ge, Weiquan Lu
Molecular Biology Reports.2012; 39(10): 9669. CrossRef
MTHFR C677T Polymorphism and Colorectal Cancer Risk in Asians, a Meta-analysis of 21 Studies
Zhen Yang, Xie-Fu Zhang, Hong-Xiang Liu, Yong-Shun Hao, Chun-Lin Zhao
Asian Pacific Journal of Cancer Prevention.2012; 13(4): 1203. CrossRef
Quantitative assessment of the association between MTHFR C677T polymorphism and colorectal cancer risk in East Asians
Shan Zhong, Jia-He Yang, Kai Liu, B. H. Jiao, Zhi-Jie Chang
Tumor Biology.2012; 33(6): 2041. CrossRef
Metabonomic Variations Associated with AOM-Induced Precancerous Colorectal Lesions and Resveratrol Treatment
Wen Liao, Hai Wei, Xiaoyan Wang, Yunping Qiu, Xiaojun Gou, Xiaolei Zhang, Mingmei Zhou, Jianbing Wu, Tao Wu, Fang Kou, Yongyu Zhang, Zhaoxiang Bian, Guoxiang Xie, Wei Jia
Journal of Proteome Research.2012; 11(6): 3436. CrossRef

Polymorphism of the 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene and Microsatellite Instability (MSI) in Mucinous Colorectal Cancer.: Kim, Hae Sol , Kang, Bong Su , Kim, Jong Woo , Ahn, Dae Ho , Bae, Su Jin , Kim, Nam Gun; J Korean Soc Coloproctol. 2008;24(5):329-336.; DOI: https://doi.org/10.3393/jksc.2008.24.5.329

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Abstract PDF

PURPOSE
Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc.
METHODS
From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses.
RESULTS
MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups.
CONCLUSIONS
The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.

Citations

Citations to this article as recorded by

Relationship between Metabolic Syndrome and MTHFR Polymorphism in Colorectal Cancer
Bong Su Kang, Dae Ho Ahn, Nam Keun Kim, Jong Woo Kim
Journal of the Korean Society of Coloproctology.2011; 27(2): 78. CrossRef

Association of Methylenetetrahydrofolate Reductase C677T, A1298C, and G1793A Polymorphism and the Risk of Colon Cancer.: Kang, Dong Baek , Rhee, Jeong Kyun , Park, Won Cheol; J Korean Soc Coloproctol. 2008;24(4):239-245.; DOI: https://doi.org/10.3393/jksc.2008.24.4.239

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1 Citations

Abstract PDF

PURPOSE
Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating folate level, which affects DNA synthesis and methylation. MTHFR is highly polymorphic, and its variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Generally, a low folate level is known to be associated with a gastrointestinal neoplasm. Three common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (C677T, A1298C and G1793A) have been reported in MTHFR. We studied the relationship of MTHFR C677T, A1298C and G1793A polymorphisms between from colon cancer group and control group of Korean people.
METHODS
We performed a case- control study to examine the relationship between MTHFR C677, A1298C, and G1793A polymorphisms and the risk of colon cancer. Two hundred seven (207) individuals with colon cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed, and (PCR-RFLP) was analyzed; as a result, MTHFR polymorphism genotypes were obtained.
RESULTS
The genotype frequencies of MTHFR C677T polymorphisms were 27.1% (CC), 48.3% (CT), 24.6% (TT), and 72.9% (CT+TT) in the patient group and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in the control group. The genotype frequencies of MTHFR A1298C polymorphisms were 58% (AA), 35.7% (AC), 6.3% (CC), and 42% (AC+CC) in the patient group and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in control group. The genotype frequencies of MTHFR G1793A polymorphisms were 83% (GG), 15.9% (GA), 1% (AA), and 16.9% (GA+AA) in the patient group and 85.8% (GG), 11.8% (GA), 2.4% (AA), and 14.2% (GA+AA) in the control group. The 677CT genotype was associated with a significantly increased risk for colon cancer (adjusted OR=1.90, 95% confidence interval: 1.25~2.90 in CT) than the 677CC genotype. The 1298CC, 1298AC, 1793AA, and 1793GA genotypes were not associated with a significantly increased risk for colon cancer.
CONCLUSIONS
The MTHFR C677T polymorphism may influence colon cancer, but the MTHFR A1298C and G1793A polymorphisms need to be studied further for careful interpretation and confirmation in larger studies.

Citations

Citations to this article as recorded by

APOE, MTHFR, LDLR and ACE Polymorphisms Among Angami and Lotha Naga Populations of Nagaland, India
Benrithung Murry, Neikethono Vakha, Nongthombam Achoubi, M. P. Sachdeva, K. N. Saraswathy
Journal of Community Health.2011; 36(6): 975. CrossRef

Distributions of MTHFR Gene Polymorphism according to the Location of Colon Cancer.: Kim, Jong Woo , Oh, Doyeun , Chong, So Young , Yim, Dong Jin , Kim, Jin Kyeoung , Kim, Nam Keun; J Korean Soc Coloproctol. 2006;22(2):69-74.

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Abstract PDF: PURPOSE
Colon carcinogenesis seems to vary according to the original location of tumor, especially theright and the left sides. Two common methylenetetrahydrofolate reductase (MTHFR) polymorphisms, 677C->T and 1298A->C, are now known. Especially, the TT type of the 677C->T mutation shows reduced catalytic activity at a rate 30% that of wild type. The aim of this study is to investigate the distributions of MTHFR polymorphisms of 677C->T and 1298A->C according to the location of the colon cancer.
METHODS
Blood samples were collected from 112 patients diagnosed in our hospital, as having colon cancer: 34 proximal and 78 distal cases to the splenic flexure and 448 healthy control subjects. In order to characterize MTHFR polymorphisms, we applied the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
The distributions of MTHFR 677C->T polymorphisms as genotypes CC, CT, and TT were 32.4%, 53.1%, and 14.5% in the control group, and 34.8%, 58.0%, and 7.1% in the cancer group (P=0.056). In the 34 proximal cancers, the CC, CT, and TT distributions were 44.1%, 55.9%, and 0% (P<0.05), respectively. In the distal group, they were 30.8%, 59.0%, and 10.3%. The distributions of the MTHFR 1298 A->C polymorphism by genotypes, AA, AC, CC were 69.6%, 28.6%, and 1.8% in the control group, and 58.9%, 38.4%, and 2.7% in the cancer group. The proximal and the distal groups show genotype distributions of 44.1%, 53.0%, and 2.9% and 65.4%, 32.0%, and 2.6%, respectively, but the differences were not statistically significant.
CONCLUSIONS
There are no definite differences between control subjects and colon-cancer patients in the two polymorphisms 677C->T and 1298A->C. However, the TT genotype shows a lower frequency in the cancer group than in the control group with a marginal statistical value (P=0.056), which suggest a reduced risk of cancer incidence for this type, compared with a CC or a CT type.

Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms in Colorectal Cancer.: Park, Won Cheol , Lee, Jeong Kyun; J Korean Soc Coloproctol. 2005;21(4):241-246.

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Abstract PDF: 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, pre-mature vascular disease, neural tube defects, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancers and gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism, and influences DNA synthesis and DNA methylation. Generally, a low folate level is known to be associated with gastrointestinal neoplasms. Also, the amino- acid-changing and enzyme-activity-reducing nucleotide polymorphism (677C-->T/Ala222Val) has been described in the MTHFR polymorphism and it brings about low enzyme activity, which may reduce DNA methylation and uracil misincorporation into DNA. These processes may be critical for the oncogenic transformation of human cells. Two common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (677C T/Ala222Val and 1298A C/Glu428Ala) have been described in MTHFR. We investigated the relation between the MTHFR C677T and A1298C polymorphisms derived from colorectal cancers and from controls in the Korean population.
METHODS
One hundred forty-eight (148) individuals with colorectal cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed by using a PCR- RFLP analysis, and MTHFR polymorphism genotypes of 677C/C, 677C/T, 677T/T, 1298AA, 1298AC, and 1298CC were obtained.
RESULTS
The genotype frequencies of MTHFR C677T polymorphisms were 25.0% (CC), 48.0% (CT), 27.0% (TT), and 75.0% (CT+TT), respectively, in case patients and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in controls. The genotype frequencies of MTHFR A1298C polymorphisms were 56.1% (AA), 372% (AC), 6.8% (CC), and 43.9% (AC+CC), respectively, in case patients and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in controls. The 677TT and the 677CT genotypes were associated with significantly increased risks for colorectal cancer (adjusted OR=1.77 and 95% CI=1.02~3.04 in TT; adjusted OR=2.07 and 95% CI=1.28~3.35 in CT) than was the 677CC, genotype but the the 1298CC and 1298 AC genotypes were not associated with significantly increased risks for colorectal cancer (adjusted OR=1.75 and 95% CI= 0.71~4.26 in CC; adjusted OR=0.95 and 95% CI=0.62~1.45 in AC).
CONCLUSIONS
The MTHFR C677T polymorphism may be influenced by colorectal cancer, but the role of the MTHFR A1298C polymorphism needs careful interpretation and confirmation in larger studies.

Case-Control Study for MTHFR and HFE Polymorphisms in Colorectal Cancer.: Lee, Ryung Ah; J Korean Soc Coloproctol. 2005;21(4):225-232.

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Abstract PDF: PURPOSE
A single nucleotide polymorphism is an important genetic variation in various pathologic situations. We examined MTHFR and HFE polymorphisms in a colorectal cancer group compared to those in a normal, healthy control group.
METHODS
Genomic DNA was isolated from whole blood of 99 colorectal cancer patients and 146 normal control patients and was subjected to MTHFR and HFE genotyping by using PCR-based restriction fragment length polymorphism analyses for the MTHFR C677T and A1298C sequences and for the HFE H63D and C282G sequences. Statistical analysis was done using SPSS 11.0.
RESULTS
The total allele frequencies of MTHFR C677T, A1298C, HFE H63D and C282Y were 0.398, 0.224, 0.014 and 0.022, respectively. The frequencies of homozygous mutants of MTHFR C677T and A1298C were 14.4% and 4.1% in the control group and 6.1% and 1.0% in the case group. There were no homozygous mutants of HFE in either group. Heterozygous mutants of H63D and C282Y were 2.1% and 4.1% in the control group and 4.0% and 5.1%, respectively in the case group. The odds ratio of a MTHFR C677T homozygous mutant was 0.604 (95% CI 0.375~0.973), and that of a MTHFR A1298C heterozygous and homozygous mutants were 0.513 (95% CI 0.298~0.883), but the difference was not statistically significant.
CONCLUSIONS
A homozygous mutant of MTHFR C677T and a homozygous and heterozygous mutant of A1298C showed a protective tendency against colorectal cancer. The HFE polymorphic mutant is quite rare in Korean population, which restricts the application of this polymorphism in a cancer epidemiologic study. The MTHFR C677T and A1298C variations should be useful predictive markers for colorectal cancer.

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