Page 242 - Vitamin D and Cancer

10 Vitamin D and Prostate Cancer 229

would be expected to reduce renal 1-alpha hydroxylation of 25-OH vitamin D
[76, 77]. One limitation of these dietary studies is the lack of consistent concur-
rent measurement of blood calcium or vitamin D levels. A recent study, [78]
however, did measure serum calcium levels and found that with serum calcium
greater than 10.2 mg/dL there was an increased risk of mortality from prostate
cancer. This was only statistically significant in sub-groups with high BMI and
when separated out for race. Along these same lines, a 2004 meta-analysis
reported an increased risk of prostate cancer with high milk consumption with
an odds ratio of 1.68 [79]. Other studies have supported the association between
high calcium intake and increased prostate cancer risk [77, 80, 81]. Consistent
with these findings, some studies have shown that high milk consumption is
associated with a reduction in circulating 1,25 vitamin D levels [76, 77].
However, these findings have not been either universal or completely consistent.
There have been multiple studies that do not show an increased risk of prostate
cancer with increased calcium intake [82–86]. Interestingly, a recent study cor-
related dietary, but not supplemental calcium intake to an increase in prostate
cancer risk [87].
Overall, dietary studies that evaluate vitamin D intake have not shown a
consistent protective effect for prostate cancer, [76, 80, 84, 88] as has been dem-
onstrated for colon cancer. This observation is consistent with the hypothesis that
loss of 1-alpha-hydroxylase activity in prostate cancer renders the tumor less sus-
ceptible to modest fluctuations of serum 25-OH vitamin D that occurs with varia-
tions in dietary intake. To the extent that circulating 1,25-OH vitamin D may be
2
important in prostate cancer, only severe vitamin D deficiency states where renal
1-alpha-hydroxylation is reduced would be expected to result in adverse cancer
outcomes.

10.5.3 Vitamin D Blood Levels and the Risk of Prostate Cancer

There are only a handful of epidemiologic studies that have measured vitamin D
levels and examined the association with risk of prostate cancer. These results
have been mixed but, in general, studies done in areas with a high prevalence
of vitamin D deficiency have shown an association between low levels of vita-
min D and subsequent development of prostate cancer. There have been 11
case–control studies that measured vitamin D and examined prostate cancer
risk (see Table 10.4).
Overall, four of the studies showed an association between decreased vitamin D
levels and increased prostate cancer risk [89–92]. Three of these studies included
subjects with a high (>50%) prevalence of vitamin D deficiency (defined as 25-OH
vitamin D < 20 ng/mL). In contrast, all of the studies that showed no association
between vitamin D blood levels and prostate cancer risk examined populations with
a much lower prevalence of vitamin D deficiency, mostly less than 20% [93–98]
and even one at zero [99].