Germ-line MTHFR C677T, FV H1299R and PAI-1 5G/4G Variations in Breast Carcinoma

Özen, Filiz; Erdiş, Eda; Sik, Ebru; Sılan, Fatma; Uludağ, Ahmet; Özdemir, Öztürk

doi:10.7314/apjcp.2013.14.5.2903

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Again similar to our results, the frequency of the TT genotype was found to be slightly increased in breast cancer patients, but this was not statistically significant [12]. The last and more recent study in a Turkish population was that by Ozen et al [13]. The T allele frequency in codon 677 was 2.3-fold and the C allele frequency 3.1-fold increased in breast cancer patients when compared to the control group.…”

Section: Discussionsupporting

confidence: 78%

“…5 studies have investigated the association between the MTHFR gene C677T polymorphism and breast cancer susceptibility in a Turkish population, however, with inconclusive results [9,10,11,12,13]. While 3 studies found that the TT genotype or T allele of the C677T polymorphism was significantly associated with an increased breast cancer risk [9,10,13], no significant association was found by the other 2 studies [11,12]. Because of these contradictory results, we decided to study the association between the MTHFR gene C677T polymorphism and breast cancer in a relatively large Turkish population.…”

Section: Introductionmentioning

confidence: 99%

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Association of the MTHFR 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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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Association of the MTHFR Gene C677T Polymorphism with Breast Cancer in a Turkish Population

et al. 2016

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“…TYMS 3′-UTR ins6/del6 showed positive association with breast cancer in the Japanese population (Zhai et al 2006), while it showed a null association in Indians (Naushad et al 2011), Chinese (Zhai et al 2006) and Germans (Justenhoven et al 2005). MTHFR C677T is the most widely studied polymorphism of this pathway; the segregation of data based on ethnic group or populations revealed a strong association of this polymorphism in Turkey (Deligezer et al 2005;Ozen et al 2013), China (Cheng et al 2008Gao et al 2009;Wu et al 2012;Jiang-Hua et al 2014), Syria (Lajin et al 2012), Morocco (Diakite et al 2012), and North America (Maruti et al 2009;Bentley et al 2010;Ramos-Silva et al 2015). Two studies, i.e., one on multi-ethnic group (Le Marchand et al 2004) and another on the Iranian population (Hosseini et al 2011), showed a protective role of this polymorphism.…”

Section: Introductionmentioning

confidence: 99%

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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“…However, studies from some Asians countries, especially from Middle East countries including Iran, Turkey, Pakistan, and Syria reported an association between breast cancer risk and the MTHFR A1298C polymorphism that suggested the C allele of this polymorphism could be a risk factor for breast cancer (35,37,39,45,46). In 2 recent meta-analyses, the MTHFR A1298C polymorphism was not a risk factor for susceptibility to breast cancer (48,49).…”

Section: Mthfr A1298c Polymorphismmentioning

confidence: 98%

“…Two further studies from Turkey observed the increased risk of breast cancer in premenopausal women in the presence of MTHFR C677T variant (37,38). Furthermore, more recent studies from Turk- ish population indicated that the MTHFR C677T was a risk factor for breast cancer (39). Also, in a population from Kazakhstan, MTHFR C677T increased the risk of breast cancer (40).…”

Section: Mthfr C677t Variants In Breast Cancermentioning

confidence: 99%

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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Germ-line MTHFR C677T, FV H1299R and PAI-1 5G/4G Variations in Breast Carcinoma

Cited by 17 publications

References 36 publications

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

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

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

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

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