Page 92 - Vitamin D and Cancer

4 The Epidemiology of Vitamin D and Cancer Risk 79

to baseline serum 25(OH)D level, with levels 80 nmol/L or higher associated with
a 72% risk reduction (95% CI = 32% to 89%) compared with levels <50 nmol/L,
P(trend) = 0.02.

4.3.2 Predicted 25(OH)D Level

Predicted 25(OH)D was examined in relation to risk of colorectal cancer in the
Health Professionals Follow-Up Study [26]. This approach required two steps.
First, plasma 25(OH)D levels were measured in a sample of 1,095 men of this
cohort. Then, factors hypothesized to influence circulating 25(OH)D levels, includ-
ing geographical region, skin pigmentation, dietary intake, supplement intake, body
mass index, and leisure-time physical activity (a surrogate of potential exposure to
sunlight UV-B) were used as the independent variables in multiple linear regression
model to develop a predicted 25(OH)D score, the dependent variable [26].
Secondly, the score, after being validated in an additional sample of men with
25(OH)D measured, was calculated for each of 47,800 cohort members and exam-
ined in relation to subsequent risk of cancer using Cox proportional hazards regres-
sion. There were 691 cases of colorectal cancer diagnosed from 1986 to 2000 in
this cohort. The analysis showed that a 25-nmol/L (10 ng/mL) increment in pre-
dicted 25(OH)D was associated with a reduced risk of colorectal cancer (multivari-
ate RR = 0.63; 95% CI 0.48–0.83), an association which persisted after controlling
for body mass index or physical activity, which are contributors to the 25(OH)D
score, and known risk factors for colorectal cancer.

4.3.3 Dietary Intake

As discussed above, dietary and supplementary intake of vitamin D are relatively
moderate predictors of 25(OH)D status, but may be relatively more important in
winter months in high latitude climates, when sunlight UV-B exposure is low.
Dietary or supplementary vitamin D has been investigated in relation to colorectal
cancer risk in cohort studies of men [27, 28] and women [29–31] or both sexes [32, 33],
as well as in case–control studies [34–41]. The majority of these studies suggested
inverse associations for colon or rectal cancer, or both endpoints combined [27–30,
33, 35, 37, 39, 40, 42]. The studies that took into account supplementary vitamin D
may be more informative as dietary vitamin D intake alone tends to be low in most
populations. For studies that also assessed supplementary vitamin D, the average
intake of the top category was approximately 700–800 IU/day, whereas in popula-
tions where vitamin D in supplements are rarely consumed, the highest intake cat-
egory averaged around 200–300 IU/day. An association with vitamin D, if one
exists, is more likely to be observed in the higher intake populations with supple-
ments assessed. In fact, in these studies, a risk reduction in the top versus bottom