B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.
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.
Xu
Xinran
X
Department of Community and Preventive Medicine, Box 1043, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Gammon
Marilie D
MD
Wetmur
James G
JG
Bradshaw
Patrick T
PT
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Santella
Regina M
RM
Chen
Jia
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014803:Vitamin B Complex / Q000008:administration & dosage*
D014803:Vitamin B Complex; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase