title: The effect of folate-related SNPs on clinicopathological features, response to neoadjuvant treatment and survival in pre- and postmenopausal breast cancer patients.
abstract: This study aimed to investigate the relationship of ten single nucleotide polymorphisms (SNPs) in the MTHFR, MTR, MTRR, DHFR, MTHFD1, TS, RFC1 and DNMT3b genes with cancer survival, therapeutic response to neoadjuvant chemotherapy and clinicopathological characteristics in 300 pre- and postmenopausal breast cancer patients of a Russian Western Siberian population. We found that the MTHFR 677CT genotype as well as combination of MTHFR 677CT and 677TT genotype was related to tumor size and estrogen-positive status in postmenopausal group. The RFC1 80А allele was associated with an increased risk of lymph node metastases among postmenopausal women. The MTHFR 677TT genotype was significantly correlated with a better progression-free survival in premenopausal patients. In contrast, a worse outcome was observed in this group patient with MTHFD1 1958AA genotype. In the multivariate analysis, the MTHFD1 1958AA genotype was identified as an independent prognostic factor for premenopausal breast cancer survival. Our findings provide evidence for associations of breast cancer survival with folate-related SNPs in a population of Western Siberian region of Russia and the MTHFD1 (1958G>A) may have additional prognostic value especially among premenopausal patients.
authors.affiliation: Department of Experimental Oncology, Cancer Research Institute of Siberian Branch of Russian Academy of Medical Sciences, Tomsk, 634050, Russian Federation. nbabyshkina@mail.ru
authors.forename: Nataliya
authors.initials: N
authors.lastname: Babyshkina
authors.forename: Elena
authors.initials: E
authors.lastname: Malinovskaya
authors.forename: Mariya
authors.initials: M
authors.lastname: Nazarenko
authors.forename: Mariya
authors.initials: M
authors.lastname: Koval
authors.forename: Polina
authors.initials: P
authors.lastname: Gervas
authors.forename: Olga
authors.initials: O
authors.lastname: Potapova
authors.forename: Elena
authors.initials: E
authors.lastname: Slonimskaya
authors.forename: Nadejda
authors.initials: N
authors.lastname: Cherdyntseva
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D017697:Premenopause; D012306:Risk
chemical_list: D015778:Minor Histocompatibility Antigens; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)