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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.

Authors: Xu, Xinran; Gammon, Marilie D; Wetmur, James G; Bradshaw, Patrick T; Teitelbaum, Susan L; Neugut, Alfred I; Santella, Regina M; Chen, Jia

Published In Cancer Epidemiol Biomarkers Prev, (2008 Aug)

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 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.

PubMed ID: 18708404 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Aged, 80 and over; Alleles; Betaine-Homocysteine S-Methyltransferase/genetics*; Breast Neoplasms/enzymology; Breast Neoplasms/genetics; Breast Neoplasms/metabolism*; Breast Neoplasms/mortality; Case-Control Studies; Cause of Death; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Logistic Models; Methylenetetrahydrofolate Reductase (NADPH2)/genetics*; Methylenetetrahydrofolate Reductase (NADPH2)/metabolism; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide/genetics; Proportional Hazards Models; Survival Analysis; Vitamin B Complex/administration & dosage*

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