Elsevier

Gynecologic Oncology

Volume 121, Issue 2, 1 May 2011, Pages 369-375
Gynecologic Oncology

Meta-analysis: Circulating vitamin D and ovarian cancer risk

https://doi.org/10.1016/j.ygyno.2011.01.023Get rights and content

Abstract

Objective

To review and summarize evidence from longitudinal studies on the association between circulating 25 hydroxyvitamin D (25(OH)D) and the risk of ovarian cancer (OC).

Methods

Relevant prospective cohort studies and nested case-control studies were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, OC incidence according to circulating vitamin D status and the respective relative risks, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing circulating vitamin D levels, all results were recalculated for an increase of circulating 25(OH)D by 20 ng/ml. Summary relative risks (RRs) were calculated using meta-analysis methods.

Results

Overall, ten individual-level studies were included that reported on the association between circulating vitamin D levels and OC incidence. Meta-analysis of studies on OC incidence resulted in a summary RR (95% confidence interval, CI) of 0.83 (0.63–1.08) for an increase of 25(OH)D by 20 ng/ml (P = 0.160). No indication for heterogeneity and publication bias was found.

Conclusions

A tentative inverse association of circulating 25(OH)D with OC incidence was found, which did not reach statistical significance but which requires clarification by additional studies due to potentially high clinical and public health impact.

Research Highlights

►As we know, this is the first systematic review and meta-analysis evaluating the association between serum 25(OH)D levels and ovarian cancer risk. ►The method for comprehensive trend estimation from summarized dose–response data was used for combining all results from individual studies so far. ►A potential weak inverse association between serum vitamin D and ovarian cancer risk was found in this meta-analysis.

Introduction

Although vitamin D is obtained from diet and dietary supplements, the main source for vitamin D is its production in the skin under the influence of solar ultraviolet B (UV-B) radiation. In 1980, Garland and Garland [1] hypothesized that lower levels of vitamin D resulting from much weaker UV-B radiation at higher latitudes may account for the striking geographical pattern of cancer mortality. Partly stimulated by this article, further research in this area has been conducted in observational studies over the past 20 years [2], [3], [4].

Several epidemiologic studies addressing the association between vitamin D and ovarian cancer (OC) have assessed dietary vitamin D intake, but results have been equivocal [5], [6], [7], [8], [9]. Most evidence from ecological studies of solar UV-B and ovarian cancer mortality and incidence support the role of vitamin D on ovarian carcinogenesis [10], [11], [12], [13], but no association was found in a multinational study [14]. In recent years, several individual-level studies have addressed the association of OC risk with circulating 25(OH)D levels representing an integrated measure for vitamin D from diet, dietary supplements, and skin production [15]. In this paper, we aimed to provide a systematic review and meta-analysis of observational epidemiological studies evaluating the association between circulating 25(OH)D levels and OC risk by using methods for comprehensive trend estimation from summarized dose–response data [16].

Section snippets

Identification of studies and study selection

A literature search was conducted to identify longitudinal studies assessing the association between circulating levels of 25(OH)D and OC incidence or mortality. We searched Ovid (Ovid Technologies, Inc., New York, 1950–August 6, 2010), EMBASE (Elsevier, Amsterdam, the Netherlands, 1980–August 16, 2010), and ISI Web of Knowledge (Thomson Scientific Technical Support, New York, 1945–August 14, 2010) databases for relevant articles by various combinations of relevant terms in the article

Results

A flow diagram of the search process is given in Fig. 1. Total searches yielded 770 entries. Following removal of 231 duplicates, 539 titles and abstracts were assessed and 22 articles appeared to be potentially relevant for inclusion into the review. 18 articles were excluded for the following reasons: no original articles but editorials, comments, reviews (N = 10), ecological studies (N = 3), only vitamin D intake reported (N = 2), only mortality among ovarian cancer patients assessed (N = 1),

Discussion

In this review and meta-analysis, we summarize the results of ten longitudinal studies published so far on the association between circulating 25(OH)D and OC incidence, which comprised a total of 2488 subjects including 883 OC cases. Although seven out of ten studies found a tentatively reduced risk of OC incidence with increasing 25(OH)D levels, none of these associations was statistically significant. The pooled estimate from our meta-analysis also suggests a possible inverse association, but

Conclusions

The results of this meta-analysis are consistent with the hypothesis of a potential weak inverse association between circulating vitamin D and OC risk. However, available data are still sparse and the tentative inverse association was not statistically significant in any of the 10 included studies, or in the meta-analysis of all studies. Nevertheless, even a modest inverse association between circulating vitamin D and OC risk in the order of magnitude estimate in this analysis could be of

Conflict of interest statement

No potential conflicts of interest were disclosed.

Acknowledgment

The work of Lu Yin was supported by a scholarship from the German Research Foundation (Deutsche Forschungsgemeinschaft) within the framework of a PhD program (Graduiertenkolleg 793).

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