Page 93 - Vitamin D and Cancer

80 E. Giovannucci

category was generally seen (risk reduction of 34% [28], 46% [29], 58% [30], 24%
[31], 30% [40], 29% male, 0% female [33], 50% males, 40% females [41], and 28%
male, 11% female [42]). In the other studies, weaker reductions or no reductions
were seen. These studies tend to support a role of vitamin D, though the high intake
groups tend to be enriched with multivitamin users and consumers of (fortified) milk
and fatty fish, which could have an anticancer effect unrelated to vitamin D.

4.3.4 Sun Exposure

Besides ecological studies that examine sun exposure (estimated by region) studies
can examine sun exposure at the individual level. One such study was a death cer-
tificate-based case–control study, which examined mortality from female breast,
ovarian, colon, and prostate cancers in relation to residential and occupational
exposure to sunlight [43]. In this study, the cases consisted of all deaths from these
cancers between 1984 and 1995 in 24 states of the USA, allowing for a very large
number of 153,511 deaths from colorectal cancer. The controls in this study were
age-frequency-matched to a series of cases, and deaths from cancer and certain
neurological diseases were excluded because of possible relationships with sun
exposure. Non-melanoma skin cancer served as a positive “control” group, and an
expected positive association was found between individuals with presumably
higher opportunity to sun exposure and skin cancer risk. The authors used multi-
variate analyses, which controlled for age, sex, race, and mutual adjustment for
residence, occupation (outdoor versus indoor), occupational physical activity levels
and socioeconomic status. For colon cancer, individuals with a high compared to
low exposure to sun based on residence were at decreased risk (RR = 0.73, 95% CI,
0.71–0.74), and individuals with outdoor occupations (RR = 0.90; 95% CI, 0.86–
0.94) and occupations that required more physical activity (RR = 0.89; 95% CI,
0.86–0.92) were at lower risk. The inverse association with outdoor occupation was
strongest among those living in the highest sunlight region (RR = 0.81; 95% CI,
0.74–0.90), suggesting that sunlight was a key factor associated with outdoor occu-
pation that reduced the risk.

4.3.5 Vitamin D and Colorectal Adenoma

Adenomas are precursors to the majority of colorectal cancers. Because adenomas
can be detected decades prior to development of cancer, they can serve as a predic-
tive indicator for cancer [44, 45]. The malignancy transformation rate for adenomas
ranges from 5% for small adenomas to 50% for villous adenomas over 2 cm in
diameter [46, 47]. Some studies have examined circulating 25(OH)D or vitamin D
intake and risk colorectal adenomas. A recent meta-analysis of colorectal adenoma,
comprised of seven studies on 25(OH)D and 12 on vitamin D intake published
before December 2007, was performed [48]. The meta-analysis found that circulating