Association of MTHFR 677C&gt;T Polymorphism with Susceptibility to Ovarian and Cervical Cancers: A Systematic Review and Meta-Analysis

Karimi-Zarchi, Mojgan; Moghimi, Mansour; Abbasi, Hajar; Hadadan, Amaneh; Salimi, Erfaneh; Morovati-Sharifabad, Majid; Akbarian-Bafghi, Mohammad Javad; Zare-Shehneh, Masoud; Mosavi‐Jarrahi, Alireza; Neámatzadeh, Hossein

doi:10.31557/apjcp.2019.20.9.2569

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…The results obtained for MTHFR 677C/T agree with those reported by other studies, 20 , 32 in that a significantly increased cancer risk was observed according to the overall analysis. However, our overall results were also inconsistent with other studies that reported no significant correlation of the MTHFR 677C/T polymorphism with an elevated risk of OC or cervical cancer in the five genetic models 33 . Additionally, although our pooled results for MTHFR 1298A/C were similar to those from a previous study, 34 they completely contradicted another study 22 when stratified by certain factors.…”

Section: Discussioncontrasting

confidence: 99%

Effects of methylenetetrahydrofolate reductase single‐nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities

Wang

Ouyang

et al. 2021

Chronic Diseases and Translational Medicine

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Background Recent studies identifying methylenetetrahydrofolate reductase ( MTHFR ) polymorphisms associated with breast cancer (BC), ovarian cancer (OC), cervical cancer, and endometrial cancer (EC) have reported conflicting results and been underpowered. To clarify the correlation between MTHFR mutations and these common female malignancies, we conducted a comprehensive meta-analysis incorporating all eligible publications. Methods Relevant reports published before January 20, 2020, were retrieved from PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval summaries for the MTHFR 677C/T and 1298A/C polymorphisms in BC, OC, cervical cancer, and EC were estimated. Results A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included. The results showed a markedly elevated risk of cancer susceptibility related to MTHFR 677C/T based on all genetic models. Similarly, we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models, except the heterozygous model. Moreover, subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models. Based on ethnicity, significant associations were observed between Asian, African, and mixed populations for 677C/T and the Asian population for 1298A/C. With regard to the sample type used for analysis, we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models. Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method, as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C, respectively. Conclusion This meta-analysis suggests that MTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers, with these findings potentially applicable for overall comparisons of related data.

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Section: Discussioncontrasting

confidence: 99%

Effects of methylenetetrahydrofolate reductase single‐nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities

Wang

Ouyang

et al. 2021

Chronic Diseases and Translational Medicine

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“…Meta-analyses, other reviews, and original papers have been describing associations of this MTHFR variant with several types of cancers, such as ovarian cancer, breast cancer, colorectal cancer, bladder cancer, lung cancer, childhood acute lymphoblastic leukemia [71][72][73][74][75][76], and even cervical cancer [77][78][79][80][81]. However, such associations remain contentious [82][83][84][85], potentially due to population differences [81]. Concerning CβS, our bibliographic survey did not reveal any study of this gene in HPV infection, cervical cancer, or precursor lesions.…”

Section: Discussionmentioning

confidence: 99%

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes

Inácio,

Aguiar,

Rodrigues

et al. 2023

Antioxidants

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Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CβS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

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“…The MTHFR 677C>T polymorphism has been the most studied, but the conclusions are still controversial. In a meta-analysis, Karimi-Zarchi et al [ 39 ] evaluated the association between MTHFR 677C>T variant and risk of ovarian and cervical cancers. A total of 27 case-control studies, including 4990 cases and 7730 controls, were selected.…”

Section: Discussionmentioning

confidence: 99%

Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers

Pawlik

Kurzawińska

Ożarowski

et al. 2023

IJMS

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We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)—well-studied functional variants involved in one-carbon metabolism—and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49–7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

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Association of MTHFR 677C>T Polymorphism with Susceptibility to Ovarian and Cervical Cancers: A Systematic Review and Meta-Analysis

Cited by 10 publications

References 41 publications

Effects of methylenetetrahydrofolate reductase single‐nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities

Effects of methylenetetrahydrofolate reductase single‐nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes

Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers

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