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

Wang, Zheng; Li, Kai; Ouyang, Liang; Hidasa, Iko; Safi, Ahmad Javid; Gao, Shan

doi:10.1016/j.cdtm.2021.06.003

Cited by 4 publications

(3 citation statements)

References 74 publications

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“…Both CβS and MTHFR did not exhibited associations with HPV infection or major lesions. 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].…”

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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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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“…In particular, increased risk has been reported for: breast cancer [52], cervical, ovarian or endometrial cancer [53], hepatocellular cancer [54], acute lymphoblastic leukemia and non-Hodgkin lymphoma in adults [55] and acute lymphoblastic leukemia in children [56].…”

Section: Cancermentioning

confidence: 99%

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

Voyer

2023

AJBSR

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Vitamin B9, folate in its natural form is present in vegetables, fruits and organ meats. The function of folate is to act in processes of transfer one carbon compounds, methylation on nucleotides, amino acids and phospholipids, processes of vital importance for cell division, synthesis of nucleic acids, amino acids and methionine from homocysteine1. Folic acid is the synthetic form most used as a supplement to compensate low intakes of folate but has not normal biological actions if it is not converted to 5-methylenetetrahydrofolate, by the enzyme methylenetetrahydrofolate reductase. This enzyme may presents polymorphism due to mutation with biotypes of varied activity. The most commonly present, C677C and A1298A, has full activity, but C677T and T677T and A1298C and C1298C with decreased activity between 30 and 70 %, can cause metabolic alterations such as hyperhomocysteinemia and DNA hypomethylation with increased risk for chromosomal abnormalities and various pathological conditions, as neural tube development disorders, early recurrent pregnancy losses, Down syndrome, cleft lip and/or palate, limb reduction, cancer, mediterranean familial fever, polycystic ovarian syndrome and neurological or cardiovascular diseases. Faced with a history of these disorders and the presence of the aforementioned enzyme biotypes, the replacement of folic acid by L 5-methylenetetrahydrofolate supplied together with vitamin B12, B2, and B6 may reduce the risk. Beside this, with excessive intakes of folic acid, especially when low activity of the enzyme is preset, high levels in the blood can be produced, with consequently higher risk of various health problems. To avoid this, recommended intakes of folic acid should not be exceeded.

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“…The polymorphism 677C>T (rs1801133) of the MTHFR gene results in decreased enzyme activity, which leads to an increase in 5,10-MTHF and a decrease in 5-MTHF. This frequently studied variant is associated with the risk of various gynecological neoplasms [ 7 ]. The variant 2756A>G (rs1805087) of the MTR gene is less studied, but it is also associated with the risk of various cancers (e.g., colorectal or thyroid) [ 8 , 9 ].…”

Section: Introductionmentioning

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

Cited by 4 publications

References 74 publications

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

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

Folate Metabolism. Polymorphisms of Methylentetrahydrofolate Reductase. Concurrent Factor in Pathogenic Effects

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

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