Page 95 - Vitamin D and Cancer

82 E. Giovannucci

Nordic countries, where the vitamin D levels may be particularly low due to low
solar UV-B exposure at higher latitudes. However, even these findings were equivo-
cal, because one of these studies also found an increased risk in men with the high-
est 25(OH)D values, which suggested a U-shaped relationship between vitamin D
and prostate cancer risk [56]. Several studies found supportive [50] or suggestive
[51] inverse associations for circulating 1,25(OH) D levels and prostate cancer risk,
2
especially for aggressive prostate cancer. In the Physicians’ Health Study, the par-
ticipants with both low 25(OH)D and 1,25(OH) D were at about a twofold higher
2
risk of aggressive prostate cancer [57]. In the Health Professionals Follow-up
Study, both lower 25(OH)D and 1,25(OH) D levels were associated with lower
2
prostate cancer risk [53], but these were mostly organ-confined prostate cancers
detected through PSA testing. In fact, although numbers of advanced cases were
limited (n = 60), there was a suggestive inverse association between 25(OH)D levels
and risk of advanced prostate cancer [53]. Finally, in the Prostate, Lung, Colorectal,
and Ovarian Cancer Screening Trial, an analysis based on 749 cases and 781 con-
trols found no association, and, in fact, even a suggestively increased risk of aggres-
sive prostate cancer among men with higher circulating 25(OH)D levels [58].
Clearly, studies of circulating 25(OH)D have tended not to support an association
for prostate cancer, or at best, have yielded equivocal results.

4.4.2 Predicted 25(OH)D Level

Predicted 25(OH)D was examined in relation to advanced stage prostate cancer in
the Health Professionals Follow-Up Study. The method for this analysis was sum-
marized above (section 4.3.2) [26]. Over follow-up from 1986 to 2002, 461 cases
of advanced prostate cancer were documented. In the multivariate model, a
25 nmol/L increment in predicted 25(OH)D level was associated with a modest
nonsignificant 20% reduction in risk, providing modest support of an association.

4.4.3 Vitamin D Intake

Only four studies were identified in the literature that examined vitamin D intake
and prostate cancer risk. None of these studies supported an association between
vitamin D intake and prostate cancer incidence [59–62]. Two of these studies
[59, 62] assessed supplemental vitamin D in addition to diet.

4.4.4 Sun Exposure

A death-certificate-based case–control study of cancer mortality described
previously for colon cancer also examined prostate cancer mortality based on