Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer
Abstract Background DNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidi...
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2025-01-01
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| author | Meng Ye Guojie Xu Liming Zhang Zhihui Kong Zhenhua Qiu |
| author_facet | Meng Ye Guojie Xu Liming Zhang Zhihui Kong Zhenhua Qiu |
| author_sort | Meng Ye |
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| description | Abstract Background DNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidines, and methyl groups. MTHFR, a key enzyme in folate metabolism, has been widely studied in relation to neural tube defects and hypertension, but its role in colorectal cancer remains underexplored. Therefore, understanding the role of folate and MTHFR genes in colorectal cancer may be helpful for potential preventive or therapeutic interventions. In this meta-analysis, the effects of MTHFR genotype and folate intake on colorectal cancer incidence were analyzed. Methods We searched PubMed,Embase, Web of Science, and CNKI database to identify relevant studies up to January 2024. We included a series of studies on the association of MTHFR C677T genotype and folate intake with colorectal cancer incidence. The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). It included 100 studies (39702 cases and 55718 controls),that investigated the association between the MTHFR C677T polymorphism and colorectal cancer (CRC). Additionally, the analysis incorporated further stratification by ethnic population and geographical region. Furthermore, Six of the studies which clarified high amount of folate might be a protective factor for CRC in all three MTHFR C677T genotype, especially in TT genotype. Results MTHFR 677TT genotype was negatively associated with CRC incidence compared with CC genotype (OR = 0.89; 95% CI: 0.85–0.93; P < 0.00001; Z = 5.17). MTHFR 677CT genotype was not significantly associated with colorectal cancer incidence (OR = 1.00; 95% CI: 0.98,1.03). A negative correlation between TT genotype and CRC was observed in ethnics of Asians (OR = 0.83, 95% CI: 0.76, 0.91), Caucasians (OR = 0.93, 95% CI: 0.88, 0.99) and the region of USA (OR = 0.77, 95% CI: 0.71, 0.85), Asia (OR = 0.93, 95% CI: 0.86, 1.00) and Europe (OR = 0.93, 95% CI:0.87, 1.00),but not in Indian (TT: OR = 1.67, 95% CI: 1.06, 2.63; CT: OR = 1.31, 95% CI: 1.00, 1.73)). Amount folate intakes might reduce the morbidity of CRC for people in MTHFR 677TT genotype (OR = 0.68; 95% CI: 0.48,0.96; P = 0.03). Conclusion The analysis showed that the incidence of colorectal cancer was reduced among individuals with TT genotype. The individuals with TT genotype and amount folate intake may collectively improve the incidence of colorectal cancer. While the MTHFR 677TT genotype is associated with a reduced risk of CRC, especially in certain populations, these findings should be interpreted with caution due to the limitations of retrospective studies. |
| format | Article |
| id | doaj-art-1cecf7f97f3945d88bf8890e8f60930f |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-1cecf7f97f3945d88bf8890e8f60930f2025-02-02T12:28:47ZengBMCBMC Cancer1471-24072025-01-0125111510.1186/s12885-025-13546-wMeta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancerMeng Ye0Guojie Xu1Liming Zhang2Zhihui Kong3Zhenhua Qiu4The First Clinical Medical College, Guangdong Medical UniversityCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe First Clinical Medical College, Guangdong Medical UniversityDepartment of Laboratory Medicine, Jingshan People’s HospitalDepartment of Laboratory Medicine, Affiliated Gaozhou People’s Hospital, Guangdong Medical UniversityAbstract Background DNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidines, and methyl groups. MTHFR, a key enzyme in folate metabolism, has been widely studied in relation to neural tube defects and hypertension, but its role in colorectal cancer remains underexplored. Therefore, understanding the role of folate and MTHFR genes in colorectal cancer may be helpful for potential preventive or therapeutic interventions. In this meta-analysis, the effects of MTHFR genotype and folate intake on colorectal cancer incidence were analyzed. Methods We searched PubMed,Embase, Web of Science, and CNKI database to identify relevant studies up to January 2024. We included a series of studies on the association of MTHFR C677T genotype and folate intake with colorectal cancer incidence. The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). It included 100 studies (39702 cases and 55718 controls),that investigated the association between the MTHFR C677T polymorphism and colorectal cancer (CRC). Additionally, the analysis incorporated further stratification by ethnic population and geographical region. Furthermore, Six of the studies which clarified high amount of folate might be a protective factor for CRC in all three MTHFR C677T genotype, especially in TT genotype. Results MTHFR 677TT genotype was negatively associated with CRC incidence compared with CC genotype (OR = 0.89; 95% CI: 0.85–0.93; P < 0.00001; Z = 5.17). MTHFR 677CT genotype was not significantly associated with colorectal cancer incidence (OR = 1.00; 95% CI: 0.98,1.03). A negative correlation between TT genotype and CRC was observed in ethnics of Asians (OR = 0.83, 95% CI: 0.76, 0.91), Caucasians (OR = 0.93, 95% CI: 0.88, 0.99) and the region of USA (OR = 0.77, 95% CI: 0.71, 0.85), Asia (OR = 0.93, 95% CI: 0.86, 1.00) and Europe (OR = 0.93, 95% CI:0.87, 1.00),but not in Indian (TT: OR = 1.67, 95% CI: 1.06, 2.63; CT: OR = 1.31, 95% CI: 1.00, 1.73)). Amount folate intakes might reduce the morbidity of CRC for people in MTHFR 677TT genotype (OR = 0.68; 95% CI: 0.48,0.96; P = 0.03). Conclusion The analysis showed that the incidence of colorectal cancer was reduced among individuals with TT genotype. The individuals with TT genotype and amount folate intake may collectively improve the incidence of colorectal cancer. While the MTHFR 677TT genotype is associated with a reduced risk of CRC, especially in certain populations, these findings should be interpreted with caution due to the limitations of retrospective studies.https://doi.org/10.1186/s12885-025-13546-wColorectal cancerMTHFRFolateMeta-analysis |
| spellingShingle | Meng Ye Guojie Xu Liming Zhang Zhihui Kong Zhenhua Qiu Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer BMC Cancer Colorectal cancer MTHFR Folate Meta-analysis |
| title | Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer |
| title_full | Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer |
| title_fullStr | Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer |
| title_full_unstemmed | Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer |
| title_short | Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer |
| title_sort | meta analysis of methylenetetrahydrofolate reductase mthfr c677t polymorphism and its association with folate and colorectal cancer |
| topic | Colorectal cancer MTHFR Folate Meta-analysis |
| url | https://doi.org/10.1186/s12885-025-13546-w |
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