MTHFR 677C&gt;T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

Singh, Pooja; Carlus, Justin; D, Sekhar; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Sanjeet; Thangaraj, Kumarasamy; Rajender, Singh

doi:10.1371/journal.pone.0120654

Cited by 16 publications

(15 citation statements)

References 75 publications

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“…The results of our meta-analysis corroborated with other meta-analyses (Yu and Chen 2012;Liang et al 2013;Castro-Quezada et al 2014); (Li et al 2014a;Rai 2014;Pooja et al 2015;Kumar et al 2015) in showing MTHFR C677T as a risk factor for breast cancer. The null association of MTR A2756G in random effects model and an inverse association with breast cancer in Caucasians were consistent with the meta-analysis of Zhong et al (2013).…”

Section: Discussionsupporting

confidence: 91%

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

et al. 2016

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Aberrations in one-carbon metabolism were reported to increase breast cancer risk by influencing the DNA synthesis and methylation of DNA and catecholamines. However, the results of these association studies remain inconclusive. We have explored the contribution of eight genetic polymorphisms in modulating the susceptibility to breast cancer by performing a meta-analysis of worldwide studies. In total, 62 case-control studies representing 17 different populations involving 18,117 breast cancer cases and 23,573 healthy controls were included in this meta-analysis. Out of the eight polymorphisms analyzed, methylenetetrahydrofolate reductase (MTHFR) C677T exhibited positive association with the breast cancer risk in both fixed effects (OR 1.14, 95 % CI 1.10-1.17) and random effects (OR 1.10, 95 % CI 1.02-1.18) models. Solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A exhibited positive association (OR 1.16, 95 % CI 1.03-1.31) while MTR A2756G exhibited an inverse association (OR 0.78, 95 % CI 0.75-0.82) with the breast in fixed effect model alone. Significant heterogeneity was observed in the association of MTHFR C677T with breast cancer even between studies from the same geographical area, specifically among Chinese, Indians, and Turks. Subgroup analysis revealed MTHFR C677T-mediated breast cancer risk in post-menopausal women and women with low dietary intake of folate. Geographical area wise segregation of data revealed MTHFR-mediated increased breast cancer risk in populations who consume methionine-rich diet. Altitude-level variations were observed in the association of SHMT1 C1420T with breast cancer. India and Brazil of same altitude showed an inverse association with this polymorphism, while USA and China that share similar altitude showed a null association. MTHFR C677T and SLC19A1 G80A are the two polymorphisms of one-carbon metabolic pathway that increase breast cancer in the worldwide population. Dietary patterns and altitudinal variations are the likely risk modulators that are contributing toward ethnic-and population-level variations in genetic associations.

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Section: Discussionsupporting

confidence: 91%

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

et al. 2016

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“…It was found that the 677C>T polymorphism is strongly associated with breast cancer in the East Asian populations [22]. Therefore, our results seem to be more relevant to other population studies: the lack of association of the MTHFR polymorphisms with the breast cancer risk was observed in Indian women [23] and in the residents of Scotland [13], Finland [24] and Greece [25].…”

Section: Resultssupporting

confidence: 60%

The polymorphisms of genes involved in DNA methylation in patients with malignancies from West Ukraine

et al. 2016

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Aim.To determine a potential role of single-nucleotide polymorphisms in genes involved in DNA methylation (MTHFR, MTR, TYMS) in the breast cancer risk and risk of leukemia in a case-control study from West Ukraine. Methods. Genotyping of MTHFR 677 C>T, MTR 2756 A>G and TS 3R2R, TS 3RG>C was performed in 60 patients with leukemia, 90 patients with breast cancer and in 100 persons from a control group. The molecular-genetic analysis was performed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism analysis. A statistical analysis was conducted by Chi-square tests and odds ratio (OR) calculation. Results. We did not observe any significant difference in genotype frequencies of the MTHFR and TYMS polymorphisms between the patients and the controls. The MTR 2756AA genotype frequency was significantly higher in the breast cancer patients vs. control (0.67 vs. 0.50, p = 0.02) while the difference between the leukemia patients and the control group was not statistically significant. The increased risk of breast cancer development was associated with the MTR 2756AA genotype (OR = 2.00, CI -95 %:1.11 -3.60) and the MTR 2756A allele (OR = 1.75, CI -95 %:1.08 -2.84). Conclusions. Our findings show that West Ukrainian inhabitants carrying at least one MTR 2756A allele have a significantly increased risk of breast cancer. K e y w o r d s: methylation, polymorphism, gene, leukemia, breast cancerBiomedicine ISSN 1993-6842 (on-line); ISSN 0233-7657 (print)

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“…Then full texts were reviewed and 2 articles (only cases) were further excluded. Based on the inclusion and exclusion criteria, finally, seventy one studies were included in the present met-analysis ( Kakkoura et al, 2015 , Lin et al, 2015 , López-Cortés et al, 2015 , Lu et al, 2015 , Singh et al, 2015 , He et al, 2014 , Huang et al, 2014 , Jiang-Hua et al, 2014 , Wang et al, 2014 , Weiwei et al, 2014 , Liu et al, 2013 , Ozen et al, 2013 , Akram et al, 2012 , Barbosa Rde et al, 2012 , Diakite et al, 2012 , Jakubowska et al, 2012 , Lajin et al, 2012 , Wu et al, 2012 , Batschauer et al, 2011 , Cerne et al, 2011 , Hosseini et al, 2011 , Hua et al, 2011 , Naushad et al, 2011 , Prasad and Wilkhoo, 2011 , Alshatwi, 2010 , Bentley et al, 2010 , Sangrajrang et al, 2010 , Vainer et al, 2010 , Wu et al, 2010 , Cam et al, 2009 , Ericson et al, 2009 , Gao et al, 2009 , Hennquez-Hernandez et al, 2009 , Jin et al, 2009 , Li and Chen, 2009 , Ma et al, 2009a , Ma et al, 2009b , Maruti et al, 2009 , Platek et al, 2009 , Yuan et al, 2009 , Cheng et al, 2008 , Inoue et al, 2008 , Kotsopoulos et al, 2008 , Langsenlehner et al, 2008 , Mir et al, 2008 , Suzuki et al, 2008 , Hekim et al, 2007 , Kan et al, 2007 , Lissowska et al, 2007 , Macis et al, 2007 , Reljic et al, 2007 , Stevens et al, 2007 ...…”

Section: Resultsmentioning

confidence: 99%

“…MTHFR gene T allele has been widely studied as a possible low-penetrance susceptibility allele for a variety of cancers, and in particular, BC. Several studies reported significant association between C677T polymorphism and BC risk ( Kakkoura et al, 2015 , Lu et al, 2015 , He et al, 2014 , Weiwei et al, 2014 , Cheng et al, 2008 ), however some other studies have reported no association between BC and C677T polymorphism ( Singh et al, 2015 , Huang et al, 2014 , Wu et al, 2012 , Ma et al, 2009a , Ma et al, 2009b ). The variation of these results might be induced by difference in ethnicities, sample size, study design and background of patients as well as random error ( Wen et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility

2015

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There are several evidences supporting the role of 5–10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk.The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst.Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03–1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02–1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06–1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01–1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03–1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06–1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99–1.14; p = 0.05).

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MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

Cited by 16 publications

References 75 publications

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

The polymorphisms of genes involved in DNA methylation in patients with malignancies from West Ukraine

Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility

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