Page 91 - Vitamin D and Cancer

78 E. Giovannucci

4.3 Colorectal Cancer

4.3.1 25(OH)D Level

Colorectal cancer has been the most frequently studied cancer in relation to vitamin D
status. Prospective studies that have examined circulating 25(OH)D levels in rela-
tion to colorectal cancer risk have tended to support a lower risk of colorectal
cancer among those with higher circulating 25(OH)D levels [13–21]. This finding
was demonstrated in a recent meta-analysis of studies of 25(OH)D level and col-
orectal cancer risk, which was based on 535 colorectal cases in total. [22]. In the
meta-analysis, individuals with serum 25(OH) level ³ 82 nmol/L had a 50% lower
incidence of colorectal cancer (p < 0.01) when compared to those with levels less
than 30 nmol/L. The two largest studies included in the meta-analysis were the
Nurses’ Health Study and the Women’s Health Initiative. In the Nurses’ Health
Study [15], based on 193 cases of colorectal cancer, the relative risk (RR) decreased
in a monotonic fashion across increasing quintiles of plasma 25(OH)D level. The
RR was 0.53 (95% confidence interval (CI) = 0.27–1.04) comparing the top to
bottom quintiles after adjusting for age, body mass index, physical activity, smok-
ing, family history, use of hormone replacement therapy, aspirin use, and dietary
intakes. The observational component of the Women’s Health Initiative (which was
also a randomized trial (RCT) of calcium and vitamin D), based on 322 total cases
of colorectal cancer, showed a similar inverse association between baseline 25(OH)D
level and colorectal cancer risk; however, detailed analyses on potential confounders
were not shown. [21].
Since this meta-analysis was reported, three additional studies on 25(OH)D and
colorectal cancer risk have been published. In the Health Professionals Follow-Up
Study [23], a nonstatistically significant inverse association between higher plasma
25(OH)D concentration and risk of colorectal cancer was observed, and a statisti-
cally significant inverse association for colon cancer (highest versus lowest quin-
tile: multivariate RR = 0.46, 95% CI = 0.24 to 0.89; P(trend) =.005). In the Japan
Public Health Center-based Prospective Study [24], a nested case–control study of
375 incident cases of colorectal cancer from 38,373 study subjects during 11.5 years
of follow-up after blood collection, plasma 25(OH)D was not significantly associ-
ated with colorectal cancer. However, the lowest category of plasma 25(OH)D was
associated with an elevated risk of rectal cancer in both men (RR = 4.6; 95%
CI = 1.0–20) and women (RR, 2.7, 95% CI, 0.94–7.6), compared with the combined
category of the other quartiles. This analysis adjusted for multiple factors, including
sex, age, study area, date of blood draw, and fasting time, smoking, alcohol con-
sumption, body mass index, physical exercise, vitamin supplement use, and family
history of colorectal cancer. Finally, 25(OH)D levels was examined in relation to
colorectal cancer mortality risk in the Third National Health and Nutrition
Examination Survey [25]. That analysis examined 16,818 participants, who were
followed from 1988–1994 through 2000, over which 66 cases of fatal colorectal
cancer were identified. The risk of colorectal cancer mortality was inversely related