In 1989, Helzlsouer et al. examined the association between serum nutrients and the development of bladder cancer. (17) They measured selenium, alpha-tocopherol, lycopene, beta-carotene, retinol, and retinol-binding protein in serum collected from 25,802 persons in Washington County, MD, in 1974. Serum samples were kept frozen at -70 degrees C. In the subsequent 12-year period, 35 cases of bladder cancer developed among participants. Comparisons of serum levels in 1974 among cases and two matched controls for each case showed that selenium was significantly lower among cases than controls (P = 0.03), lycopene was lower among cases at a borderline level of significance (P = 0.07), and alpha-tocopherol was nonsignificantly lower (P = 0.13). For selenium there was a nearly linear increase in risk with decreasing serum levels (P = 0.03). When examined by tertiles, the odds ratio associated with the lowest tertile of selenium compared to the highest tertile was 2.06. Serum levels of retinol, retinol-binding protein, and beta-carotene were similar among cases and controls. The researchers concluded that these results support a role for selenium in the prevention of bladder cancer.
In 2002, Zeegers et al. reported an inverse association between toenail selenium level and bladder cancer risk in a case-cohort analysis from the Netherlands Cohort Study. (79)
As discussed earlier in new studies since the FDA granted a qualified health claim for selenium and cancer, in 2006, a case-control study was undertaken by Kellen et al. to quantitatively determine if low selenium levels were associated with increased risk of bladder cancer. (66) Eight epidemiological studies examined the association between serum selenium concentration and bladder cancer risk. A population case-control study in 178 cases and 362 controls was carried out to assess the relationship between bladder cancer risk and selenium serum concentrations. Unconditional logistic regression was calculated to determine odds ratios (OR) for bladder cancer occurrence with corresponding 95% confidence intervals (95% CI). Effect modification by smoking status, low fruit and vegetable intake, retinol equivalent, vitamin C, vitamin E and total antioxidant status were also assessed. The results were that serum selenium level was negatively associated with bladder cancer risk. After adjustment for sex, age, smoking and occupational exposure, the OR was 0.48 (95% CI 0.29-0.79) comparing the second with the lowest tertile (serum selenium concentration >82.40 mcg/L). The adjusted OR for the highest tertile (serum selenium concentration >96.00 mcg/L), was 0.30 (95% CI 0.17-0.52) (P-trend <0.001). An increase of 10 mcg/L in serum selenium concentration was associated with a significant decreased bladder cancer risk (OR: 0.76; 95% CI 0.67-0.85). The researchers concluded that this case-control study demonstrated an inverse association between serum selenium concentration and bladder cancer risk. (66)
The SU.VI.MAX Intervention trial did not list the bladder cancer data per se, but grouped cancers of the urinary tract together. (55) The SU.VI.MAX data show that there was a reduced rate of urinary cancers in men taking the selenium and antioxidant supplements. The rate per 100,000 person years was 37 vs. 44.