Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development

Lopes, Tairine Zara; Gimenez-Martins, A. P. A.; Nascimento-Filho, Carlos H. V.; Castanhole-Nunes, Márcia Maria Urbanin; Galbiatti-Dias, Ana Lívia Silva; Padovani-Júnior, João Armando; Maníglia, José Victor; Francisco, José Luís Esteves; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria

doi:10.4238/gmr.15028222

Cited by 17 publications

(9 citation statements)

References 28 publications

(55 reference statements)

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“…Alterations in DNA methylation due to MTHFR polymorphisms may be associated with the development of cancer [74][75][76]. Association studies on MTHR C677T polymorphisms and BC risk were performed in Brazil [77] and Ecuador [78] (Table 5). In both reports, the authors found a significant association between this SNP and BC risk.…”

Section: Other Bc Susceptibility Mutations In Central and South Amerimentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

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Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate-and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

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Section: Other Bc Susceptibility Mutations In Central and South Amerimentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

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“…It has been suggested that the cancer risk associated with MTHFR polymorphisms may be modulated by alcohol intake, but only a few previous studies have examined this issue in detail regarding thyroid cancer risk. A similar Brazilian study was recently conducted to determine the interaction between alcohol consumption and MTHFR C677T on thyroid cancer risk, but the interactive effect was not statistically significant ( P for interaction = 0.84) 38 . The inconsistency between the Brazilian study and the current study may be due to differences in genetic characteristics of the studied populations, which may affect certain biochemical reactions after alcohol consumption; for instance, the ALDH2 genetic variant is prevalent only in East Asians and is associated with an inability to metabolize a carcinogenic alcohol metabolite, acetaldehyde, into acetate 39 .…”

Section: Discussionmentioning

confidence: 99%

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea

Yang

Lee

Park

et al. 2018

Sci Rep

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The effect of alcohol intake on thyroid cancer is unestablished, and its interaction effects with genetic susceptibility are unclear. In this case-control study, the relationship among alcohol intake, the methylenetetrahydrofolate reductase (MTHFR) gene, and thyroid cancer risk has been evaluated. In total, 642 cases and 642 controls of Korean origin were included, and the genetic variants C677T and A1298C of the MTHFR gene were analysed. The interactions between alcohol-consumption behaviour and genetic variants were analysed with a likelihood ratio test, wherein a multiplicative interaction term was added to a logistic regression model. There was an independent association between the C677T polymorphism and thyroid cancer risk but not for drinking history. For C677T C/C homozygotes, individuals with a history of alcohol consumption showed a protective OR (95% CI) of 0.42 (0.15–1.13) when never drinkers were used as the reference. However, this protective association was not observed among individuals with a T+ allele with an OR (95% CI) of 1.27 (0.89–1.82), showing different directions for the association between genotypes with a significant interaction (Pinteraction = 0.009). Based on the genetic characteristics of individuals included, an interaction between alcohol intake and MTHFR C677T may modify the risk of thyroid cancer.

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“…Thus, exposure to inorganic arsenic may deplete the pool of methyl groups and interfere with folate metabolism with consequences on DNA synthesis and repair. The reduced expression of MTHFR has been previously associated with breast cancer development (53). Conversely, in this study, we noted in MCF7 cells in culture that exposure to NaAs III had a biphasic effect on the expression of FOLR1, a membrane-bound protein involved in transport of folate into cells.…”

Section: Discussionmentioning

confidence: 99%

Arsenic‑induced BRCA1 CpG promoter methylation is associated with the downregulation of ERα and resistance to tamoxifen in MCF7 breast cancer cells and mouse mammary tumor xenografts

et al. 2019

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A significant percentage (~30%) of estrogen receptor-α (ERα)-positive tumors become refractory to endocrine therapies; however, the mechanisms responsible for this resistance remain largely unknown. Chronic exposure to arsenic through foods and contaminated water has been linked to an increased incidence of several tumors and long-term health complications. Preclinical and population studies have indicated that arsenic exposure may interfere with endocrine regulation and increase the risk of breast tumorigenesis. In this study, we examined the effects of sodium arsenite (NaAsIII) exposure in ERα-positive breast cancer cells in vitro and in mammary tumor xenografts. The results revealed that acute (within 4 days) and long-term (10 days to 7 weeks) in vitro exposure to environmentally relevant doses reduced breast cancer 1 (BRCA1) and ERα expression associated with the gain of cyclin D1 (CCND1) and folate receptor 1 (FOLR1), and the loss of methylenetetrahydrofolate reductase (MTHFR) expression. Furthermore, long-term exposure to NaAsIII induced the proliferation and compromised the response of MCF7 cells to tamoxifen (TAM). The in vitro exposure to NaAsIII induced BRCA1 CpG methylation associated with the increased recruitment of DNA methyltransferase 1 (DNMT1) and the loss of RNA polymerase II (PolII) at the BRCA1 gene. Xenografts of NaAsIII-preconditioned MCF7 cells (MCF7NaAsIII) into the mammary fat pads of nude mice produced a larger tumor volume compared to tumors from control MCF7 cells and were more refractory to TAM in association with the reduced expression of BRCA1 and ERα, CpG hypermethylation of estrogen receptor 1 (ESR1) and BRCA1, and the increased expression of FOLR1. These cumulative data support the hypothesis that exposure to AsIII may contribute to reducing the efficacy of endocrine therapy against ERα-positive breast tumors by hampering the expression of ERα and BRCA1 via CpG methylation, respectively of ESR1 and BRCA1.

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Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development

Cited by 17 publications

References 28 publications

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea

Arsenic‑induced BRCA1 CpG promoter methylation is associated with the downregulation of ERα and resistance to tamoxifen in MCF7 breast cancer cells and mouse mammary tumor xenografts

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