Vitamin D may protect against several
cancers, but data about the association between circulating
vitamin D and
bladder cancer are limited. Within the
Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-
tocopherol and β-
carotene supplements on
cancer incidence in male smokers, 250
bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of
bladder cancer by a priori categories of baseline serum
25-hydroxyvitamin D [25(
OH)D; i.
e., <25, 25 to <37.5, 37.5 to <50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(
OH)D was associated with a statistically significantly increased risk of
bladder cancer (versus ≥50 nmol/L; <25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to <37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to <50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend=0.04). Similarly, increased risks for the lowest
vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend=0.03). In this prospective study of male smokers, lower serum 25(
OH)D was associated with an increased risk of
bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women.