Xu Xinran, Gammon Marilie D, Wetmur James G, Bradshaw Patrick T, Teitelbaum Susan L, Neugut Alfred I, Santella Regina M, Chen Jia
Department of Community and Preventive Medicine, Box 1043, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2109-16. doi: 10.1158/1055-9965.EPI-07-2900.
Breast cancer is the second leading cause of cancer mortality among women. Given its important role in DNA methylation and synthesis, one-carbon metabolism may affect breast cancer mortality. We used a population-based cohort of 1,508 women with breast cancer to investigate possible associations of dietary intake of B vitamins before diagnosis as well as nine polymorphisms of one-carbon metabolizing genes and subsequent survival. Women newly diagnosed with a first primary breast cancer in 1996 to 1997 were followed for vital status for an average of 5.6 years. Kaplan-Meier survival and Cox proportional hazard regression analyses were used to evaluate the association between dietary intakes of B vitamins (1,479 cases), genotypes ( approximately 1,065 cases), and all-cause as well as breast cancer-specific mortality. We found that higher dietary intake of vitamin B(1) and B(3) was associated with improved survival during the follow-up period (P(trend) = 0.01 and 0.04, respectively). Compared with the major genotype, the MTHFR 677 T allele carriers have reduced all-cause mortality and breast cancer-specific mortality in a dominant model [hazard ratio (95% confidence interval): 0.69 (0.49-0.98) and 0.58 (0.38-0.89), respectively]. The BHMT 742 A allele was also associated with reduced all-cause mortality [hazard ratio, 0.70 (0.50-1.00)]. Estrogen receptor/progesterone receptor status modified the association between the MTHFR C677T polymorphism and survival (P = 0.05). The survival associations with one-carbon polymorphisms did not differ with the use of chemotherapy, although study power was limited for examining such effect modification. Our results indicate that one-carbon metabolism may be an important pathway that could be targeted to improve breast cancer survival.
乳腺癌是女性癌症死亡的第二大主要原因。鉴于其在DNA甲基化和合成中的重要作用，一碳代谢可能会影响乳腺癌死亡率。我们使用了一个基于人群的队列，其中包括1508名乳腺癌女性患者，以研究诊断前B族维生素的饮食摄入量以及一碳代谢基因的九种多态性与后续生存之间的可能关联。对1996年至1997年新诊断为原发性乳腺癌的女性进行了平均5.6年的生命状态随访。采用Kaplan-Meier生存分析和Cox比例风险回归分析来评估B族维生素饮食摄入量（1479例）、基因型（约1065例）与全因死亡率以及乳腺癌特异性死亡率之间的关联。我们发现，较高的维生素B1和B3饮食摄入量与随访期间生存率的提高相关（趋势P值分别为0.01和0.04）。与主要基因型相比，MTHFR 677 T等位基因携带者在显性模型中全因死亡率和乳腺癌特异性死亡率降低[风险比（95%置信区间）：分别为0.69（0.49 - 0.98）和0.58（0.38 - 0.89）]。BHMT 742 A等位基因也与全因死亡率降低相关[风险比，0.70（0.50 - 1.00）]。雌激素受体/孕激素受体状态改变了MTHFR C677T多态性与生存之间的关联（P = 0.05）。尽管研究效能有限，无法检验这种效应修饰，但一碳多态性与生存的关联在化疗使用方面并无差异。我们的结果表明，一碳代谢可能是一个重要途径，可作为改善乳腺癌生存的靶点。
