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

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Summary

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.

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Authors and Affiliations

  1. Department of Medicine, Division of Internal Medicine, Vanderbilt School of Medicine, Vanderbilt University, Nashville

    Martha J. Shrubsole, Xiao Ou Shu, Qiuyin Cai, Hui Cai, Qi Niu & Wei Zheng

  2. Vanderbilt Center for Health Services Research, Vanderbilt University Medical Center, Nashville

    Martha J. Shrubsole, Xiao Ou Shu, Qiuyin Cai, Hui Cai, Qi Niu & Wei Zheng

  3. Vanderbilt-Ingram Cancer Center, Nashville, Tennessee

    Martha J. Shrubsole, Xiao Ou Shu, Qiuyin Cai, Hui Cai & Wei Zheng

  4. VA TN Valley Geriatric Research, Education, and Clinical Center (GRECC), Nashville, TN

    Martha J. Shrubsole, Xiao Ou Shu, Qiuyin Cai & Wei Zheng

  5. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

    Zhi Xian Ruan & Yu-Tang Gao

  6. Center for Health Services Research, Division of Internal Medicine, Department of Medicine, School of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-1121 Medical Center North, Nashville, TN, 37232-2587

    Martha J. Shrubsole

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  1. Martha J. Shrubsole
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Correspondence to Martha J. Shrubsole.

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Shrubsole, M.J., Shu, X.O., Ruan, Z.X. et al. MTHFR genotypes and breast cancer survival after surgery and chemotherapy: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat 91, 73–79 (2005). https://doi.org/10.1007/s10549-004-7265-6

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  • DOI: https://doi.org/10.1007/s10549-004-7265-6

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