Page 320 - Vitamin D and Cancer

13 Vitamin D and Colorectal Cancer 307

course of decades. As such, a 7 year treatment period may be insufficient to
detect a protective effect for vitamin D, especially if vitamin D effects are
limited to the earlier steps in the carcinogenesis process. Finally, there was no
limitation or control process on the population enlisted on the WHI study in
regards to their vitamin D intake. Indeed, the average vitamin D intake in this
population was estimated at 367 IU/day at the time of enrollment and rose
further during the conduct of the study. Vitamin D intake on the WHI study was
estimated as double the national average [45]. It is possible that the increased
baseline vitamin D intake on the WHI study washed out any potential protective
effects of the study supplementation.
It is fair to conclude from the WHI study that a low dose of vitamin D supple-
mentation is not effective in preventing colorectal cancer. However, the effective-
ness of higher doses of vitamin D in preventing colorectal cancer is still an open
question. Based on our studies and those of others in the literature, a dose of
2,000 IU/day or higher may be needed to adequately investigate a role for vitamin D
protection in colorectal cancer (see below).

13.3 Vitamin D Status in Advanced Colorectal Cancer

Little is known about vitamin D status in patients with advanced colorectal cancer.
One study has assessed 25-D levels across a small number of patients with stages
3
I-IV colon cancer who had not received any chemotherapy treatment. No signifi-
cant difference was noted in 25-D levels across different stages [82]. We have
3
evaluated 25-D levels in more than 300 patients with colorectal cancer with stage
3
II-IV disease and in various stages of treatment. Patients were stratified according
to age, body mass index (BMI), season of blood draw, location of their primary
tumor, stage of disease (I-III vs. IV), and chemotherapy status (no chemotherapy,
or chemotherapy within 3 months from 25-D level draw) [83]. Vitamin D defi-
3
ciency was common among patients with colorectal cancer with a median 25-D
3
level of 21.3 ng/mL. On multivariate analysis, only primary site of disease and
chemotherapy status were associated with very low 25-D levels (£15 ng/mL).
3
Chemotherapy was associated with a fourfold increase in risk of severe vitamin D
deficiency while a rectal primary was associated with a 2.6-fold increase. This
suggests that chemotherapy may increase the risk of vitamin D deficiency in
patients with colorectal cancer. The etiology of the increased 25-D deficiency with
3
chemotherapy is under current investigation. Possible etiologies include decreased
vitamin D absorption secondary to chemotherapy-induced gastrointestinal toxicity
or modulation of 25-D hydroxylation. These retrospective findings, if validated in
3
prospective settings, suggest that patients with colorectal cancer may require more
aggressive vitamin D supplementation in the setting of chemotherapy in compari-
son to a prevention setting. This may be particularly important given recent sugges-
tions that vitamin D status impacts the overall survival of patients with established
colorectal cancer [84, 85].