Page 88 - Vitamin D and Cancer

4 The Epidemiology of Vitamin D and Cancer Risk 75

level. Before the specific studies are reviewed, the major strengths and limitations
of the various approaches to assess vitamin D status that have been used will be
summarized.

4.2 Overview of Study Designs

4.2.1 Prospective Studies of Circulating 25(OH) Vitamin D
and Cancer Risk

Some studies have examined plasma or serum 25(OH) level in relation to cancer
risk, especially for colorectal cancer and for prostate cancer. There are a few other
studies for other endpoints, including breast, ovarian, and pancreatic cancers. The
studies based on circulating 25(OH)D level are arguably the “gold standard” among
observational studies for testing the vitamin D cancer hypothesis because 25(OH)
D accounts not only for skin exposure to UV-B radiation, but also for factors that
determine vitamin D status, such as total vitamin D intake and skin pigmentation.
In addition, 25(OH)D has a relatively long half-life (t ) in the circulation of about
1/2
2–3 weeks, and thus can provide a fairly good indicator of long-term vitamin D
status. For example, in one study of middle-aged to elderly men, the correlation of
two 25(OH)D measures approximately 3 years apart was 0.7 [9]. However, it is not
clear how the consistency of 25(OH)D over time would be across other
populations.
In epidemiologic studies, circulating 25(OH)D has typically been based on a
measure in archived blood samples using a nested case–control study design.
Because the sample is taken before the diagnosis of cancer, in some cases over a
decade before, it is unlikely that any association observed is due to reverse causa-
tion, that is, spuriously due to the cancer influencing the blood level. One complexity
in studies of 25(OH)D is that typically only one measurement is made, and levels
fluctuate seasonally throughout the year due to variances in sun exposure. Several
studies have been based on the measurement of 25(OH)D in individuals already
diagnosed with cancer; these studies need to be interpreted very cautiously because
of the potential for the phenomenon of reverse causation. For example, during treat-
ment period for cancer, exposure to sunlight is likely to be very skewed due to
hospitalizations, disability, change in habit, etc. Thus, these types of studies are not
summarized in detail here.

4.2.2 Studies of Vitamin D Intake

Vitamin D intakes are relatively low in general because of the scarcity of vitamin D
in natural foods and fortification of this vitamin is limited. For example, a glass