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B-Vitamin Intake, One-Carbon Metabolism, and Survival in a Population-Based Study of Women with Breast Cancer

Departments of ¹ Community and Preventive Medicine, ² Microbiology, ³ Genetics and Genomic Sciences, ⁴ Pediatrics, and ⁵ Oncological Science, Mount Sinai School of Medicine; Departments of ⁶ Epidemiology, ⁷ Medicine, and ⁸ Environmental Health Sciences, Columbia University, New York, New York; and ⁹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Requests for reprints: Jia Chen, Department of Community and Preventive Medicine, Box 1043, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. Phone: 212-241-7519; Fax: 212-360-6965. E-mail: jia.chen{at}mssm.edu

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 (1,065 cases), and all-cause as well as breast cancer–specific mortality. We found that higher dietary intake of vitamin B₁ and B₃ 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. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2109–16)