Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study

Abstract

Two common polymorphisms in the MTHFR gene, C677T and A1298C, are associated with reduced enzyme activity and may be associated with breast cancer susceptibility.We performed a case-control study to investigate the association between the two SNPs in the MTHFR gene and risk of breast cancer. In total, 58 breast cancer patients and 58 unaffected controls were enrolled in the study. Polymerase chain reaction/restriction fragment length polymorphism technique (PCR-RFLP) was conducted to determine the genotypes.No significant differences were found in the genotypes of the two polymorphisms of the MTHFR gene between cases and controls. The OR and 95% CI for the 677CC, 677CT and 677TT genotypes were 1.00, 0.95 (0.39-2.31) and 0.87 (0.27-2.80), respectively; those of the 1298AA, 1298AC and 1298CC genotypes were 1.00, 0.59 (0.26-1.36) and 0.78 (1.32-4.66) respectively. Furthermore, it has been shown in patients with breast cancer a risk of presenting with an aggressive biophenotype about twice or three times higher in the presence of the C677T and A1298C polymorphisms, respectively. Finally, the A1298Cpolymorphism is significantly associated with increased recurrence risk of lymph node-positive breast cancer.Our study has not shown a significant association between MTHFR gene polymorphisms and breast cancer risk. However, it highlighted the key-role played by the presence of mutant alleles for both polymorphisms in increasing the risk of developing more aggressive phenotypes; moreover, specifically in A1298C, it might also lead to a higher risk of developing lymph node metastasis.

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia

“…Our study compared to the previous one [23], with the study groups carefully selected regarding ethnicity, greater sample size and with a control group without the auto-selection bias, showed no evidence of association between the MTHFR-rs1801133 and rs1801131 and the clinicopathological variables.…”

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

“…The association of the biophenotype and polymorphisms highlighted the risk of presenting a more aggressive biophenotype two or three times higher in patients with the C677T and A1298C polymorphisms, respectively, suggesting an association of the polymorphisms with tumor progression. Additionally, the group also showed an association of the A1298C polymorphism with the risk of lymph node metastasis and an increased risk of developing BC in patients with polymorphic homozygous (CC) genotypes and overweight individuals [ 84 ]. However, Houghton et al did not observe a significant association between polymorphisms and BC, although relating the presence of the polymorphism to plasma folate levels has shown a strong relationship with BC.…”

Association of C677T (rs1081133) and A1298C (rs1801131) Methylenetetrahydrofolate Reductase Variants with Breast Cancer Susceptibility Among Asians: A Systematic Review and Meta-Analysis

“…In a total of 19 studies on 15,628 subjects, it was revealed that another polymorphism, rs1801131 (A1298C), located in exon 7 of the MTHFR gene (Castiglia et al 2019), was significantly associated with BC in homozygous and allelic models, even though no significant difference was found in recessive, dominant, heterozygous, and overdominant models. Interestingly, the subgroups analysis seemed to suggest that genetic models of recessive, dominant, heterozygous, homozygous, and allelic in participants from Western Asia were significantly associated with the risk of BC.…”

“…Another common SNP, A1298C (rs1801133), transforms glutamate to alanine at 429 residues and reduces enzyme activity (Wan et al 2018). Similar to C677T, there is still controversy as to the association of this mutation with BC, particularly in Asian population (Castiglia et al 2019;Kaya et al 2016).…”