Vitamin D and prevention of colorectal cancer

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Abstract

Background

Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence rates of colorectal cancer, but the dose–response relationship has not been adequately studied.

Methods

Dose–response gradients from observational studies of Vitamin D intake and serum 25-hydroxyvitamin D were plotted as trend lines. The point on each linear trend line corresponding to an odds ratio of 0.50 provided the prediagnostic Vitamin D intake or 25-hydroxyvitamin D concentration associated with 50% lower risk compared to <100 IU/day Vitamin D or <13 ng/ml serum 25-hydroxyvitamin D. Medians of these values were determined.

Results

Overall, individuals with ≥1000 IU/day oral Vitamin D (p < 0.0001) or ≥33 ng/ml (82 nmol/l) serum 25-hydroxyvitamin D (p < 0.01) had 50% lower incidence of colorectal cancer compared to reference values.

Conclusions

Intake of 1000 IU/day of Vitamin D, half the safe upper intake established by the National Academy of Sciences, was associated with 50% lower risk. Serum 25-hydroxyvitamin D of 33 ng/ml, which is known to be safe, also was associated with 50% lower risk. Prompt public health action is needed to increase intake of Vitamin D3 to 1000 IU/day, and to raise 25-hydroxyvitamin D by encouraging a modest duration of sunlight exposure.

Introduction

Markedly higher mortality rates from colon cancer in the northeast and lower rates in the south, southwest and west led to the development of a theory that Vitamin D and calcium reduce the risk of colon cancer [1]. Maps of the geographic epidemiology of colon cancer played a key role in making the discovery that Vitamin D reduced risk [1], [2]. Since the theory was advanced, four observational studies [3], [4], [5], [6] have provided data on the dose–response relationship between serum 25-hydroxyvitamin D (25(OH)D) and risk of colorectal cancer, and 14 observational studies [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20] have provided data on the dose–response gradient of oral intake of Vitamin D with risk.

Despite findings that in general support the Vitamin D-cancer theory, and a powerful geographic gradient by latitude [2] the overall dose–response gradient for the effect of Vitamin D on incidence of colorectal cancer has not been determined. Understanding of the dose–response relationship is needed to enhance decision-making about the emerging role of Vitamin D as a tool for reducing incidence and mortality from colorectal cancer.

Section snippets

Materials and methods

A systematic review was conducted of published studies that provided sufficient data to calculate the dose–response relationship of serum 25(OH)D or oral intake of Vitamin D with risk of colorectal cancer.

Analysis of studies

A majority (10 of 18) studies found that inadequate Vitamin D status was significantly associated with higher risk of cancer of the colon [3], [6], [7], [8], [9], [10], [12], [13], [15] or distal colon and rectum [5], one found a borderline association of low Vitamin D intake with elevated risk of colorectal cancer after multivariate adjustment [11], one found an non-significant odds ratio of 0.4 for the highest quartile of 25(OH)D compared to the lowest and no significant dose–response

Strengths

This review was based on all studies that were identified through a MEDLINE search and it has a larger overall sample size than any study or review of this field. Many of the dose–response relationships that were used to identify the ED50 for Vitamin D or 25(OH)D were linear. The largest serum 25(OH)D study, that of the Nurses Health Study Cohort by Feskanich et al. [6] (Section 3.2.4; Fig. 4), had the clearest dose–response relationship, and it was linear. The same cohort, provided a clear

Acknowledgements

This research was supported by a Congressional allocation to the Hollings Cancer Center of the Medical University of South Carolina, Charleston, SC, through the Department of the Navy, Bureau of Medicine and Surgery, under Work Unit No. 60126. The views expressed in this report are those of the authors and do not represent an official position of the Department of the Navy, Department of Defense, or the U.S. Government. Approved for public release; distribution unlimited. The authors are

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