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Unformatted text preview: B-vitamin Intake, One-carbon Metabolism and Survival among a Population-based Study of Women with Breast Cancer Xinran Xu 1 , Marilie D. Gammon 6 , James G. Wetmur 2,3 , Patrick T. Bradshaw 6 , Susan L. Teitelbaum 1 , Alfred I. Neugut 7,8 , Regina M. Santella 9 , and Jia Chen 1,4,5,* 1 Departments of Community and Preventive Medicine, Mount Sinai School of Medicine 2 Department of Microbiology, Mount Sinai School of Medicine 3 Departments of Genetics and Genomic Sciences, Mount Sinai School of Medicine 4 Department of Pediatrics, Mount Sinai School of Medicine 5 Department of Oncological Science, Mount Sinai School of Medicine 6 Department of Epidemiology, University of North Carolina at Chapel Hill 7 Department of Epidemiology, Columbia University. 8 Department of Medicine, Columbia University. 9 Department of Environmental Health Sciences, Columbia University. Abstract 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 utilized a population-based cohort of 1,508 women with breast cancer to investigate possible associations of dietary intake of B vitamins prior to diagnosis as well as 9 polymorphisms of one- carbon metabolizing genes and subsequent survival. Women newly diagnosed with a first primary breast cancer in 1996-1997 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 (1479 cases), genotypes ( 1065 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 for trend = 0.01 and 0.04, respectively). Compared to the major genotype, the MTHFR 677 T allele carriers have reduced all- cause mortality and breast cancer-specific mortality in a dominant model [HR and 95% CI: 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 [HR 0.70(0.50-1.00)]. ER/PR 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. Keywords one-carbon; diet; B vitamin; gene polymorphism; breast cancer; survival *Corresponding author [J.C.] and to whom requests for reprints should be addressed at 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: E-mail: firstname.lastname@example.org....
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