To investigate the incidence of breast cancer and prediagnostic serum level
s of folate, B12, and pyridoxal 5'-phosphate (B6), we conducted a nested ca
se-control study using resources from the Washington County (Maryland) seru
m bank, In 1974, 12,450 serum specimens were donated, and in 1989, 14,625 p
lasma specimens were donated by female residents of Washington County. One
hundred ninety-five incident breast cancer cases and 195 controls were matc
hed by age, race, menopausal status at donation, and cohort participation a
s well as by date of blood donation. In both cohorts and all menopausal sub
groups, median B12 concentrations were lower among cases than controls, Dif
ferences reached statistical significance only among women who were postmen
opausal at donation (1974 cohort, 413 versus 482 pg/ml, P = 0.03; 1989 coho
rt, 406 versus 452 pg/ml, P = 0.02), Among women postmenopausal at blood do
nation, observed associations of B12 suggested a threshold effect with incr
eased risk of breast cancer in the lowest one-fifth compared to the higher
four-fifths of the control distribution [lowest versus highest fifth: 1974
cohort, matched odds ratio = 4.00 (95% confidence interval = 1.05-15.20); 1
989 cohort, matched odds ratio = 2.25 (95% confidence interval = 0.86-5.91)
]. We found no evidence for an association between folate, B6, and homocyst
eine and breast cancer, Findings suggested a threshold effect for serum B12
with an increased risk of breast cancer among postmenopausal women in the
lowest one-fifth compared to the higher four-fifths of the control distribu
tion, These results should stimulate further investigations of potentially
modifiable risk factors, such as these B-vitamins, for prevention of breast
cancer.