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

Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

doi:10.1016/j.mgene.2015.08.008

Cited by 41 publications

(34 citation statements)

References 113 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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“…A decreased methylation pattern may cause uncontrolled gene expression and genomic instability, and induce carcinogenesis [19,20]. To date, a lot of studies have reported on the association between the MTHFR gene C677T polymorphism and breast cancer; however, results have remained controversial [21,22]. …”

Section: Discussionmentioning

confidence: 99%

“…In recent years, 2 large meta-analyses about the MTHFR gene C677T polymorphism and breast cancer were published [21,22]. The first analyzed 41 studies; 4 of these were from Turkey and included 16,480 breast cancer patients and 22,388 controls [21].…”

Section: Discussionmentioning

confidence: 99%

“…The results of the second meta-analysis including 75 studies (5 from Turkish populations) with 31,315 cases and 35,608 controls suggested a moderately significant association between the MTHFR gene C677T polymorphism and breast cancer (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) [22]. A subgroup analysis based on ethnicity showed a strongly significant association between the TT genotype and breast cancer (TT vs. CC, OR = 1.26, 95% CI 1.06-1.51, p = 0.009) in Asian populations; however, such an association was not observed in Caucasian populations including Turkey (TT vs. CC, OR = 1.08, 95% CI 0.99-1.14, p = 0.05).…”

Section: Discussionmentioning

confidence: 99%

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Association of the <b><i>MTHFR</i></b> Gene C677T Polymorphism with Breast Cancer in a Turkish Population

et al. 2016

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Background: Breast cancer is the most common cancer among women. 1 in every 8 women in the United States have a lifetime risk of getting breast cancer. MTHFR is a key enzyme that regulates the folate metabolism which has an important role in DNA synthesis, repair, and methylation. The aim of the current study was to analyze the association between the MTHFR gene C677T (Ala222Val, rs1801133) polymorphism and breast cancer. Patients and Methods: 199 breast cancer patients and 195 healthy controls were included in this study. The MTHFR gene C677T polymorphism was analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. A meta-analysis including 707 breast cancer patients and 880 controls from Turkish populations was also carried out. Statistical analyses were performed using the χ² test. Results: No statistically significant differences in allele and genotype frequencies were observed between patients and controls (p > 0.05). Although not statistically significant, TT homozygous variants were encountered more frequently in patients than in controls. A statistically significant association was observed between the MTHFR gene C677T polymorphism and the tumor histology of breast cancer patients (p = 0.038). The results of the meta-analysis suggested that there was a high association between breast cancer and the MTHFR gene C677T polymorphism in Turkish populations (p < 0.0001). Conclusion: In our study, we did not find any association between the MTHFR gene C677T polymorphism and breast cancer. However, a meta-analysis of the 6 association studies carried out in Turkish populations with 707 patients and 880 controls showed a significant association between breast cancer and the MTHFR gene C677T polymorphism.

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“…The latter meta-analysis suggested the risk of breast cancer was significantly associated with postmenopausal status (48). Also, 3 recent meta-analyses suggested a significant relation between MTHFR 677TT genotype and breast cancer risk in Asian populations (49)(50)(51). The association of MTHFR C677T polymorphism with hypomethylation of DNA might suggest a role for this polymorphism in development of cancer.…”

Section: Mthfr C677t Variants In Breast Cancermentioning

confidence: 93%

Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Variants, Folate Intake, and Susceptibility to Breast Cancer

2017

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Context: Breast cancer is the most common cancer among women, worldwide. Both genetic and environmental factors are involved in the risk of breast cancer. Folate is an essential nutrient that is involved in DNA synthesis, repair, and methylation. Single nucleotide polymorphisms (SNPs) in folate related genes, such as methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are suitable candidates for investigation the role of these variants in susceptibility to breast cancer.Evidence Acquisition: Using the relevant English language studies from the search engines, such as MEDLINE/PubMed, EMBASE, and Scopus from 2005 to 2016, the present review looks at the role of MTHFR C677T and A1298C variants, synergism between these gene variants along with folate intake in susceptibility to breast cancer. Results:It seems the MTHFR C677T polymorphism is associated with the risk of breast cancer among Asians but not in Caucasians. However, the MTHFR A1298C polymorphism might not be a susceptibility factor for breast cancer. The MTHFR haplotypes alone or along with low dietary intake of folate were not involved in susceptibility to breast cancer. Conclusions:Association between MTHFR C677T polymorphism with the risk of breast cancer could be attributed to the lower activity of the MTHFR enzyme in the presence of 677T allele with reduced availability of folate that may result in uracil misincorporation in the DNA and cancer development. The absence of establishment of a role for MTHFR haplotypes and a synergism between low dietary intake of folate along with MTHFR polymorphisms in susceptibility to breast cancer might be due to differences in allelic frequency of MTHFR variants in various populations, stage of cancer, the familial and early onset cancer, and the influence of environmental factors. To establish the role of MTHFR haplotypes in relation to folate intake in susceptibility to breast cancer, more studies with adequate sample size that investigate the role of MTHFR gene polymorphisms along with dietary intake of folate in the risk of breast cancer are necessary. Keywords: MTHFR C677T, MTHFR A1298C, B Vitamins, Breast Cancer ContextBreast cancer is the most common cancer among women, worldwide (1) that comprises 16% of all female cancers (2). Around 235,303 new cases of breast cancer, and about 40,430 deaths per year have been reported in the United States (3). In developed countries, this cancer comprises approximately 10% of all cancers and 23% of women cancers (4). The incidence of breast cancer is increasing in developing countries with a rate of 3% to 4% (5) and the breast cancer is appeared around 1 decade earlier than that in developed countries. Early detection of breast cancer reduces the mortality rates and improves patient prognosis (1).The etiology of breast cancer is not well known, but a family history of the disease, genetic background, high level of estrogen, reproduction history, age at menarche and menopause, dietary habit, life style, cigarette smoking, age, and alcohol consumption are s...

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

Cited by 41 publications

References 113 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

Association of the <b><i>MTHFR</i></b> Gene C677T Polymorphism with Breast Cancer in a Turkish Population

Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Variants, Folate Intake, and Susceptibility to Breast Cancer

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