Serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma recurrence

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Abstract

There is strong epidemiological and laboratory evidence that vitamin D may be protective against colorectal neoplasia. Therefore, we sought to assess the relationship between serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma recurrence in our ursodeoxycholic acid trial. A total of 568 participants were randomly selected for analysis of serum 25(OH)D levels. The range of total 25(OH)D was 5.5–66.1 ng/ml, with a median of 25.6 ng/ml. After categorizing 25(OH)D levels into tertiles based on the population distribution, the adjusted odds ratios (95% CI) for adenoma recurrence in the second and third tertiles were 0.88 (0.56–1.39) and 0.78 (0.49–1.24), respectively. The association between serum 25(OH)D and adenoma recurrence appeared to be stronger among women than men. As compared to those below the median value, women with serum 25(OH)D levels above the median had an OR (95% CI) of 0.59 (0.30–1.16); the corresponding OR (95% CI) for men was 0.95 (0.60–1.49). Analyses by dietary vitamin D intake revealed no statistically significant associations. In summary, the results of this study show a moderate, nonsignificant inverse association between serum 25(OH)D levels and reduced risk for colorectal adenoma recurrence, particularly among women.

Introduction

Colorectal cancer is one of the most common cancers in the United States, and it is estimated that up to 75% of these cancers could be avoided by implementation of dietary changes [1]. This has led to intensive study of the dietary risk factors for colorectal cancer. Epidemiological and clinical researchers have sought to investigate the potential association between vitamin D and risk of colorectal neoplasia. Low serum levels of 25(OH)D were found to be significantly associated with risk of both colorectal adenoma [2] and cancer [3] in two large cohort studies. Some studies have found an inverse nonsignificant association between dietary or total intake of vitamin D and colorectal adenomas or cancer [4], [5], [6], [7], while others have not [8], [9]. The most recent contribution to the vitamin D and colorectal neoplasia literature are results from the Women's Health Initiative (WHI) [10]. In this randomized, double-blind placebo-controlled trial of 36,282 women, participants were assigned to a supplement of 500 mg of calcium carbonate plus 200 IU of vitamin D3 twice daily, or a placebo. The results showed that the intervention had no appreciable effect on colorectal cancer; however, in a nested case–control analysis, those within the lowest quartile of serum 25(OH)D levels at baseline had a significantly increased risk for development of colorectal cancer. Therefore, the association between 25(OH)D levels and risk for colorectal neoplasia remains equivocal. We sought to assess the relation between these levels and risk for colorectal adenoma recurrence in a study population residing in an area with high exposure to sunlight.

Section snippets

Study population and design

Study participants were drawn from the ursodeoxycholic acid (UDCA) trial, a phase III, double-blind, randomized, placebo-controlled trial designed to assess the effect of UDCA treatment (8–10 mg/kg day) for three years on risk of colorectal adenoma recurrence. Study participants were recruited from four clinics throughout Tucson and Phoenix, were aged 40–80, and had one or more adenomas removed within the 6 months prior to randomization. No effect of UDCA on recurrence of adenomatous polyps was

Results

Table 1 presents a comparison of all participants in the UDCA trial (n = 1192) with the randomly-selected subset of participants (n = 568) that had serum analyzed for 25(OH)D. Characteristics between the two groups were similar, with the exception of the rate of colorectal adenoma recurrences. For all UDCA participants, the percentage of those with recurrences was 42.3, while for those in the subset it was 36.8. Because those colonoscopies that occurred prior to the blood draw were excluded from

Discussion

The results of the current study show a moderate, non-significant inverse association between serum 25(OH)D levels and risk for colorectal adenoma recurrence. This relationship appeared to be stronger for women than for men, although an interaction term for 25(OH)D and gender was not statistically significant. Colonoscopies were used to ascertain adenoma recurrence events. In order to maintain a prospective design, we first excluded data from all colonoscopies that occurred prior to the blood

Conclusion

We found a moderate, nonsignificant inverse association between serum 25(OH)D levels and colorectal adenoma recurrence that was confined to women. Future work will include investigation of effect modification by vitamin D receptor and retinoid x receptor polymorphisms.

Acknowledgements

We would like to extend our gratitude to Julie Buckmeier, Carole Kepler, and Janine Einspahr for their efficient and dedicated efforts for this project.

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Supported in part by Public Health Service grants (CA-41108, CA-23074, and CA-77145), and the Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancer (CA95060). Dr. Jacobs is supported by a Career Development Award from the National Cancer Institute (1K07CA10629-01A1).

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