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Background  Folate plays a pivotal role in DNA synthesis, repair, methylation and homocysteine (Hcy) metabolism. Therefore, alterations in the folate-mediated one-carbon metabolism may lead to abnormal methylation proliferation, increases of tumor/neoplasia and vein thrombosis/cardiovascular risk. The serine hydroxymethyhransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) regulate key reactions in the folate and Hcy metabolism. Therefore, we investigated whether the genetic variants of the  SHMT, MS, MTRR  and  CBS g ene can affect plasma Hcy levels and are associated with breast cancer risk.    Methods  Genotyping was performed by PCR-RFLP method. Plasma Hcy levels were measured by the fluorescence polarization immunoassay on samples of 96 cases and 85 controls.    Results  (a) The  SHMT 1420 T, MS 2756G, MTRR 66G  allele frequency distribution showed significant difference between case and controls (p < 0.01 ~ 0.05). (b) The concentration of plasma Hcy levels of  SHMT 1420TT  was significantly lower than that of the wild type, while the plasma Hcy levels of  MS 2756GG ,  CBS 699TT/1080TT  significantly higher than that of the wild type both in case and controls. The plasma Hcy levels of  MTRR 66GG  was significantly higher than that of wild type in cases. The plasma Hcy levels of the same genotype in cases were significantly higher than those of controls except  SHMT 1420CC, MS 2756AA, MTRR 66GG ; (c) Multivariate Logistic regression analysis showed that  SHMT C1420T  (OR = 0.527, 95% CI = 0.55 ~ 1.24),  MS A2756G  (OR = 2.32, 95% CI = 0.29 ~ 0.82),  MTRR A66G  (OR = 1.84, 95% CI = 0.25 ~ 1.66) polymorphism is significantly associated with breast cancer risk. And elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 4.45, 95% CI = 1.89-6.24 for the highest tertile as compared with the lowest tertile).    Conclusions  The current study results seem to suggest a possibility that S HMT C1420T  mutation may be negatively correlated with breast cancer susceptibility; while  MS A2756G  and  MTRR A66G  mutation may be positively associated with breast cancer risk.  SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T  locus mutation may be factors affecting plasma levels of Hcy. The plasma Hcy levels could be metabolic risk factor for breast cancer risk to a certain extent.

Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women