Increased breast cancer risk has been observed with both low folate status and a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR 677C --> T). Cytoplasmic serine hydroxymethyltransferase (cSHMT) affects the flow of one-carbon units through the folate metabolic network, but there is little research on a role for genetic variation in cSHMT in determining breast cancer risk. A nested case-control study within the Nurses' Health Study was used to investigate an association between cSHMT (1420C --> T) and breast cancer risk. No evidence for an association between the cSHMT genotype and breast cancer was observed. There was also no evidence of a gene-gene interaction between cSHMT and MTHFR. There was no evidence of an association between the cSHMT genotype and breast cancer occurrence. Further research in populations with differing average folate intake may be required to fully understand the interactions of folate nutrition, sequence variation in folate genes and breast cancer risk.
