In this nested case-control study within the Multiethnic Cohort, we did not observe a significant association between plasma 25(OH)D levels and prostate cancer risk overall. Indeed, we observed a nonsignificant increased risk of total prostate cancer for high 25(OH)D concentration (≥50 ng/ml). We found no significant associations with advanced or high grade cancer.
An IARC Working Group conducted a meta-analysis of 7 prospective studies, and found no association between circulating 25(OH)D and prostate cancer; the relative risk for an increase of l ng/ml unit of serum 25(OH)D was 0.998 (95% CI = 0.992-1.005).17
Adding the present study, as well as other recent prospective studies showing no association between circulating 25(OH)D and prostate cancer in Finnish men8
and in the European Prospective Investigation into Cancer and Nutrition22
would clearly not alter the result of this meta-analysis. In fact, two studies observed an increased risk with higher 25(OH)D levels, especially for more aggressive disease, 7,23
which was contrary to the hypothesis that vitamin D is protective against prostate cancer.
Plasma 25(OH)D concentrations in our study population (33.1 ng/ml in the controls) were higher than reported for the US male population covering similar age groups: 24.8 ng/ml in men 50-69 years and 24.0 ng/ml in men ≥70 years.24
Using the cutoff of 20 ng/ml,21
16.1 % of our study subjects would be considered vitamin D deficient, which is lower than in the general US male population (27.0% of men 50-69 years and 26.6% of men ≥70 years).24
However, since methods for assessment of blood 25(OH)D have not been standardized, such comparison between studies may not be reliable.17
Nonetheless, since our subjects are residents in Hawaii and California (primarily Los Angeles County) where sunlight is abundant all year round, circulating vitamin D levels might be expected to be higher than in men living at higher latitudes. Thus, it is possible that we did not observe any association between 25(OH)D and prostate cancer because of the small number of participants with low plasma 25(OH)D concentrations. For instance, Ahonen and colleagues12
found an elevated risk of prostate cancer only for men with 25(OH)D levels below 16 ng/ml, whereas only 6.9% of our subjects had such low levels.
Racial/ethnic differences in 25(OH)D concentrations among our study population are consistent with other reports for the US population; for example, non-Hispanic whites had higher concentrations than did Mexican Americans and non-Hispanic Blacks.25
This is also consistent with the fact that people with more extensive skin pigmentation have lower plasma 25(OH)D concentrations.18
When we examined African American men separately, who had the lowest mean values of 25(OH)D and the largest number of cases in our study (n = 136), we still did not observe any effect of low vitamin D status on prostate cancer development (OR for <20 vs. ≥30 ng/ml = 1.03, 95% CI = 0.64-1.66). However, it is premature to draw any conclusions regarding race/ethnic-specific associations in this study due to the limited number of cases in each ethnic group for the different exposure levels. Few other studies examined circulating vitamin D levels related to prostate cancer risk among non-White populations. Another study of Japanese Americans living in Hawaii, in which the median concentration of 25(OH)D (41.6 ng/ml) was higher than in the Japanese men in our study (median = 34.4 ng/ml), found no association between vitamin D metabolites and prostate cancer risk.13
The study's strengths include a prospective design, which minimized the chance that the disease influenced health-related behaviors (such as dietary practices and screening for prostate cancer) in the cases, and participants with diverse racial/ethnic backgrounds. Nevertheless, there are several limitations to consider. We measured 25(OH)D using only a one-time plasma sample and thus it may not reflect long-term circulating vitamin D status. However, a validation study has shown a relatively high correlation coefficient (0.70) for two measures of 25(OH)D over a three year period.10
The majority of the cases had early stage disease which limited our ability to detect an effect of circulating 25(OH)D on tumor progression. Also, statistical power was limited for race/ethnic-specific analyses, due to the limited number of cases. The time between blood draw and tumor diagnosis (mean = 1.9 years) was relatively short, and thus preclinical disease might have influenced circulating vitamin D status in some cases.
In conclusion, findings from this prospective study of men in the Multiethnic Cohort do not support the hypothesis that vitamin D protects against prostate cancer. Further follow-up is warranted to determine whether the findings are consistent across ethnic groups.