MTHFR genotypes and breast cancer survival after surgery and chemotherapy: a report from the Shanghai Breast Cancer Study.

摘要

Methylenetetrahydrofolate reductase (MTHFR) regulates the intracellular folates pool for DNA synthesis and methylation. Sequence variations in MTHFR (nucleotides 677 (C-->T) and 1298 (A-->C)) result in allozymes with decreased activity. The 677TT genotype is associated with increased toxicity of methotrexate and increased clinical response to 5-fluorouracil in treatment of cancers including breast cancer. We evaluated MTHFR genotypes and breast cancer survival in a cohort of 1067 Chinese women diagnosed with breast cancer between 1996 and 1998 who received surgery and chemotherapy. Life table method was used to calculate 5-year survival rates. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for potential confounding factors. Median follow-up time was 5.2 years; 5-year survival was 84.6%. Sixty-six percent carried a 677T allele and 31% carried a 1298 C allele. We found that overall 5-year breast cancer survival did not differ significantly across all genotypes (85.3% for 677 CC and 83.8% for 677TT; 83.8% for 1298 AA and 79.1% for 1298 CC). However, carrying the 677T allele was associated with non-significant increased risk of death for subjects with late stage disease (stages III-IV) (HR=1.80, 95% CI: 0.79-4.14 for TT vs. CC, p for trend=0.15), particularly among those who had survived past the second year (HR=2.97, 95% CI: 1.10-7.98, p for trend=0.04). The A1298C genotypes were not significantly associated with risk of death. This study suggests that the MTHFR C677T polymorphisms may affect long-term survival from advanced breast cancer.