The MTHFR C677T polymorphism, estrogen exposure and breast cancer risk: a nested case-control study in Taiwan.

BACKGROUND We evaluated the effects of the MTHFR C677T polymorphism and its interaction with estrogen exposure on breast cancer risk in a nested case-control study conducted in Taiwan. MATERIALS AND METHODS A total of 88 histologically confirmed breast cancer cases and 344 cancer-free controls were recruited between July 1992 and December 2000. The MTHFR C677T genotype was determined by a PCR-RFLP-based assay. All subjects completed in-person interviews. RESULTS There was a significant trend of breast cancer in relation to prolonged exposure to estrogens prior to the first full-term pregnancy (FFTP) (p for trend = 0.0015). In contrast, there was no statistically significant association between the risk of breast cancer and the MTHFR C677T genotype. However, a significantly elevated risk of breast cancer predisposed by the MTHFR 677T variant genotype (CT and TT) was observed in women with prolonged exposure to estrogens prior to FFTP (adjusted OR = 4.98, 95% CI = 2.00-12.43). CONCLUSION The results of this study suggest that the MTHFR 677T variant genotype per se may have no overall association with breast cancer risk, but a sizable association could be observed in the presence of relevant environmental exposure.