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184 S.A. Mazzilli et al.

with 1,25(OH) D post UV-B exposure only. The treatment of 1,25(OH) D pre and
2 3 2 3
post UV-B exposure appeared to reduce the amount of DNA damage as measured
by the number of cyclobutane pyrimidine dimers (CPDs) formed. Further examina-
tion into the efficacy of vitamin D as a preventive agent is required, however the
current study begins to shed a positive light for a preventive mechanism for
melanoma.
Retinoblastoma is common in children that has relatively high cure rates [32].
However, although treatments are successful they are often destructive and may
cause visual impairment, thus finding methods to prevent progression may reduce
the impairments associated with treatment. A study by Albert et al. examines the
potential for the use of 1,25(OH) D in the prevention of retinoblastoma in a trans-
2 3
genic mouse model of retinoblastoma [33]. The retinoblastoma transgenic mice
express SV40 T antigen in the retina, which inactivates the p 105 protein resulting
Rb
in the formation of ocular tumors beginning at 14 weeks of age [34]. 8–10 week old
mice were treated with either 0.05 mg or 0.025 mg of 1,25(OH) D five times a
2 3
week for 5 weeks then sacrificed at 5 months age. In mice treated with high dose
1,25(OH) D , 20% had no evidence of disease while the remaining had organ con-
2 3
fined disease. In the mice treated with low dose 1,25(OH) D , 13% had no evidence
2 3
of disease. In contrast, all untreated mice formed bilateral disease that involved
large invading tumors. This model clearly demonstrates that 1,25(OH) D inhibits
2 3
the growth and local extension of retinoblastoma, suggesting a potential preventive
role for vitamin D for retinoblastoma.

8.2.6 Summary

Overall the preclinical studies support a chemopreventive role for vitamin D in
cancer. More studies are needed to understand the impact of vitamin D deficiency
on cancer initiation and progression. Likewise, more information is needed to
define sufficient levels of vitamin D necessary to achieve an anticancer benefit as
well as defining the optimal levels for achieving the greatest anticancer benefit.
A greater understanding of the molecular mechanism by which vitamin D exerts its
chemopreventive effects and defining the molecular phenotype of the target cells
that respond to vitamin chemoprevention therapy will enhance our ability to effec-
tively utilize vitamin D and its analogs to reduce the incidence and impact of can-
cers in the clinic.

8.3 Clinical Prevention Trials

While the epidemiology of vitamin D status has been associated with lower cancer
rates, supported by preclinical research, there have been only a few clinical preven-
tion trials in humans that appear in the literature. These trials are included in the