Page 94 - Vitamin D and Cancer

4 The Epidemiology of Vitamin D and Cancer Risk 81

25(OH)D was inversely associated with risk of total colorectal adenoma (RR = 0.70
(95% CI: 0.56–0.87, for high versus low circulating 25(OH)D) and advanced ade-
noma (RR = 0.64, 95% CI: 0.45–0.90). In addition, the highest quintile of vitamin D
intake was associated with a decreased risk of colorectal adenoma compared to low
vitamin D intake (RR = 0.89; 95% CI: 0.78–1.02), recurrent adenoma (RR = 0.88;
95% CI: 0.72–1.07), and advanced adenoma (RR = 0.75, 95% CI: 0.57–0.99). The
overall results of this meta-analysis indicate that vitamin D status, assessed through
intake and circulating 25(OH)D, is associated with a decreased risk of colorectal
adenoma, especially advanced adenoma.

4.3.6 Randomized Controlled Trial

The Women’s Health Initiative was a randomized placebo-controlled trial that
examined 400 IU vitamin D plus 1,000 mg/day of elemental calcium in 36,282
postmenopausal women in relation to risk of colorectal cancer (n = 322 cases) and
other endpoints over 7 years [21]. This study found no suggestion of a benefit of
the intervention on incidence of colorectal cancer, but this trial had some important
limitations, which preclude a definitive answer. First, and most importantly, the
dose of 400 IU/day of vitamin D was likely insufficient to yield a meaningful con-
trast of 25(OH)D between the treated and the control groups. The anticipated
increase of circulating 25(OH)D level following an increment of 400 IU/day would
be approximately 7.5 nmol/L, and was likely even less given the suboptimal com-
pliance in this study. In the epidemiologic studies of 25(OH)D, the contrast between
the high and low quintiles was generally at least 50 nmol/L (20 ng/mL) [22].
Second, epidemiologic data, although limited, suggest that any influence of vitamin D
(and calcium) intakes may require at least 10 years to demonstrate a risk reduction
for colorectal cancer [30], so possibly the time duration of the trial may not have
been sufficiently long. Third, the Women’s Health Initiative study had a factorial
design with hormonal replacement use, and a post hoc analysis suggested an inter-
action whereby women who had not taken hormones may have benefited from the
vitamin D and calcium intervention, but those on hormones did not [49]. If so, the
effect of vitamin D may have been diluted in the overall study population.

4.4 Prostate Cancer

4.4.1 25(OH) Vitamin D

Most of the studies of circulating 25(OH)D level and prostate cancer risk have not
found clear risk reductions for prostate cancer associated with higher 25(OH)D
levels, although some of the studies suggested weak inverse associations [20, 50–54].
The only two studies [55, 56] that support an inverse association were conducted in