Polymorphisms in the MTHFR Gene Are Associated with Breast Cancer

Abstract

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a χ² analysis indicated that the MTHFR 677T allele was significantly distributed (χ² = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.

Genetic polymorphisms in the one‐carbon metabolism pathway and breast cancer risk: A population‐based case–control study and meta‐analyses

“…Similarly, a meta-analysis including data from our study and 12 previously published studies 5,6,8,9,13,14,27,28 showed no evidence for an overall association for MTHFR E429A (summary OR 5 1.00; 95% CI 0.85-1.17 based on 6,521 cases and 8,515 controls; Table III). Results were similar across racial groups and geographical regions.…”

“…16 The Polish population is ethnically homogenous, which minimizes concerns about population stratification. We did not study all key genes in the 8 Lee et al 11 , Ergul et al, 27 Justenhoven et al, 28 Deligezer et al 33 and this study.- 3 Studies included in meta-analysis for MTHFR A222V in postmenopausal women: Le Marchand et al (all subpopulations combined), 8 Forsti et al, 9 Lee et al, 11 Justenhoven et al, 28 Deligezer et al 33 and this study.- 4 Studies included in meta-analysis for MTHFR E429A in premenopausal women: Le Marchand et al (all subpopulations combined), 8 Ergul et al, 27 Justenhoven et al 28 and this study. 8 Justenhoven et al 28 and this study.…”

“…A meta-analysis including data from this study and 21 previously published studies [5][6][7][8][9][10][11][12][13][14][27][28][29][30][31][32][33] showed no association between variant vs. common homozygote genotypes for MTHFR A222V and breast cancer risk [summary OR (95% CI) 5 0.99 (0.86-1.15), based on 8,330 cases and 10,825 controls]. Similarly, a meta-analysis including data from our study and 12 previously published studies 5,6,8,9,13,14,27,28 showed no evidence for an overall association for MTHFR E429A (summary OR 5 1.00; 95% CI 0.85-1.17 based on 6,521 cases and 8,515 controls; Table III).…”

Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study

“…Previous studies revealed higher risk of breast and esophagus cancer but not colorectal cancer with less functional forms of MTHFR (Ergul et al, 2003;Stolzenberg-Solomon et al, 2003;Pardini et al, 2011). The MTHFR gene is located at the end of the short arm of chromosome 1 (1p36.3) (Goyette et al, 1998).…”

Breast Cancer in Morocco: A Literature Review

“…MTHFR gene plays an important role in the genomic integrity and DNA biosynthesis leading to genetic instability and increasing the risk of several cancers including breast cancer (Ergul et al, 2003).…”