Abstract
Abstract Background: Breast cancer is a heterogeneous disease, comprising several molecular subtypes with diverse biological behavior, clinical presentations and responses to therapy. Given the important role that folate plays in the availability of methyl groups and in the synthesis and repair of DNA, we examined the relationship between single nucleotide polymorphisms in folate-related genes MTHFR (677C>T, 1298A>C), MTR (2756A>G), MTRR (66G>A), DHFR del19, MTHFD1 (1958G>A), TS (28-bp repeat, 1494del6), RFC1 (80G>A), DNMT3b (149C>T) with therapeutic response to neoadjuvant chemotherapy of breast cancer patients according to molecular subtypes. Material and methods: This study included 300 patients with histologically diagnosed primary breast cancer who were treated between 1998 and 2008 at the Tomsk Cancer Research Institute. Subgroups were classified on the basis of ER, PR, and HER2 immunohistochemical evaluation. PCR-RFLP analysis was used to determine the MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, MTRR 66G>A, MTHFD1 1958G>A and DNMT3b 149C>T polymorphisms. Genotyping for the DHFR del19, TS 28-bp repeat and TS 1494del6 were based on polymerase chain reaction. Results: A trend was detected towards accumulation of the MTHFD1(AA) and RFC1(GG) genotypes in triple negative (TN) cases compared with the luminal A group (P = 0.06 and P = 0.07 respectively). In addition, we observed that the DHFR(del19/del19) and MTRR(GA) genotypes tended to show an association with HER2+ subtype (P = 0.06 and P = 0.09 respectively). We found that the TN women carrying MTRR(GG) genotype had a worse clinical response to neoadjuvant chemotherapy compared to luminal A cases but this difference did not reach statistical significance (P = 0.06). Luminal A subtype group with MTHFD1(AA) genotype showed an association with better response to neoadjuvant chemotherapy in comparison TN patients (P=0.03). Conclusion: Our study indicates that the analysis of folate-related gene polymorphisms may help to identify patient subgroups at high risk for the progression of breast cancer. MTHFD1 (1958G>A) may be considered as a molecular marker associated with more aggressive tumor behavior such as TN cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C101.
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