Int J Med Sci 2019; 16(8):1089-1095. doi:10.7150/ijms.32162 This issue

Research Paper

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

Paolo Castiglia1*, Valeria Sanna2*, Antonio Azara1, Maria R. De Miglio1, Luciano Murgia1, Giovanna Pira1, Francesca Sanges1, Alessandro Fancellu1, Ciriaco Carru3, Marco Bisail4, Maria Rosaria Muroni1✉

1. Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella, 4 - 07100 Sassari, Italy.
2. Division of Medical Oncology, AOU Sassari, Via E. De Nicola - 07100 Sassari, Italy; Sassari, Italy.
3. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43 - 07100 Sassari, Italy.
4. LILT, Sassari, Via Amendola, 40/L - 07100 Sassari, Italy.
*Equal contributors

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Castiglia P, Sanna V, Azara A, De Miglio MR, Murgia L, Pira G, Sanges F, Fancellu A, Carru C, Bisail M, Muroni MR. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study. Int J Med Sci 2019; 16(8):1089-1095. doi:10.7150/ijms.32162. Available from

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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.

Keywords: Methylenetetrahydrofolate reductase (MTHFR), Folate, Polymorphisms, SNPs C677T and A1298C, Breast cancer.