Research article
Optimal Vitamin D Status for Colorectal Cancer Prevention: A Quantitative Meta Analysis

https://doi.org/10.1016/j.amepre.2006.11.004Get rights and content

Background

Previous studies, such as the Women’s Health Initiative, have shown that a low dose of vitamin D did not protect against colorectal cancer, yet a meta-analysis indicates that a higher dose may reduce its incidence.

Methods

Five studies of serum 25(OH)D in association with colorectal cancer risk were identified using PubMed. The results of all five serum studies were combined using standard methods for pooled analysis. The pooled results were divided into quintiles with median 25(OH)D values of 6, 16, 22, 27, and 37 ng/mL. Odds ratios were calculated by quintile of the pooled data using Peto’s Assumption-Free Method, with the lowest quintile of 25(OH)D as the reference group. A dose–response curve was plotted based on the odds for each quintile of the pooled data. Data were abstracted and analyzed in 2006.

Results

Odds ratios for the combined serum 25(OH)D studies, from lowest to highest quintile, were 1.00, 0.82, 0.66, 0.59, and 0.46 (ptrend<0.0001) for colorectal cancer. According to the DerSimonian-Laird test for homogeneity of pooled data, the studies were homogeneous (chi2=1.09, df=4, p=0.90. The pooled odds ratio for the highest quintile versus the lowest was 0.49 (p<0.0001, 95% confidence interval, 0.35–0.68). A 50% lower risk of colorectal cancer was associated with a serum 25(OH)D level ≥33 ng/mL, compared to ≤12 ng/mL.

Conclusions

The evidence to date suggests that daily intake of 1000–2000 IU/day of vitamin D3 could reduce the incidence of colorectal with minimal risk.

Introduction

The Women’s Health Initiative1 demonstrated that a low dose of vitamin D did not protect against colorectal cancer within 7 years of follow-up; however, a meta-analysis indicates that a higher dose may reduce its incidence.

There were approximately 145,300 new cases and 56,300 deaths from colorectal cancer in the United States during 2005.2 An observation of higher age-adjusted mortality rates of colorectal cancer in the northern and northeastern United States compared to the southwest, Hawaii, and Florida led to a theory that vitamin D of mainly solar origin may reduce risk of colorectal cancer3 through a mechanism involving calcium metabolism, intercellular adherence, and contact inhibition. Since then, five observational studies have explored the association of serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D (25[OH]D) with risk of colorectal cancer.1, 4, 5, 6, 7 However, an overall dose–response gradient for the effect of serum levels of 25(OH)D on colorectal cancer risk has not been determined. This meta-analysis provides an estimated dose–response gradient that may be of help in planning for a useful role of vitamin D in control of colorectal cancer.

Section snippets

Study Inclusion

The PubMed database was searched for the period from January 1966 to December 2005 by using the terms (“vitamin D,” or “25-hydroxyvitamin D”), and (“cohort” or “case–control” or “case–cohort” or “incidence” or “occurrence” or “epidemiology”) and “human” as medical subject heading (MeSH) terms and words in the abstract. Articles were included if they were published in medical journals and included measures of association by quantile. A total of five studies were identified and all five met the

Results

Five studies of the association of serum 25(OH)D with risk of colorectal cancer were identified.1, 4, 5, 6, 7 All were nested case–control studies of prediagnostic serum collected from healthy volunteer donors who were then followed from 2–25 years for incidence (Table 1). Three studies reported statistically significant trends toward lower odds ratios in individuals with higher levels of 25(OH)D,1, 6, 7 while two reported trends in the same direction that were of borderline significance or not

Discussion

A meta-analysis increases power by combining the results of many studies. All known published studies of serum 25(OH)D and risk of colorectal cancer were included, and the results were homogenous. Pooling of such independent studies increases precision, because random fluctuation in any one study tends to be counterbalanced by results of other studies.

The data from two different studies of serum 25(OH)D in the Johns Hopkins cohort in Washington County MD had trends that were uneven but

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