Elsevier

Preventive Medicine

Volume 46, Issue 4, April 2008, Pages 298-302
Preventive Medicine

Review
Vitamin D and calcium intake in relation to risk of endometrial cancer: A systematic review of the literature

https://doi.org/10.1016/j.ypmed.2007.11.010Get rights and content

Abstract

Objective

In response to a recent ecologic study of UV exposure and endometrial cancer incidence, we present the epidemiologic evidence on the relation between intake of vitamin D and its metabolically related nutrient, calcium, and the occurrence of endometrial cancer.

Methods

We conducted a systematic literature review and meta-analysis of vitamin D and calcium in relation to endometrial cancer, including peer-reviewed manuscripts published up to May 2007. Random and fixed effects summary estimates were computed.

Results

Pooled analyses of the three case-control studies of dietary vitamin D and endometrial cancer uncovered heterogeneous results that were not significant in random or fixed effects analyses. Cut-points for the highest vitamin D intakes ranged from > 244 to > 476 IU/day. Qualitatively similar findings were observed for dietary calcium. Only two studies provided estimates for calcium supplements (random effects OR = 0.62, 95% CI 0.39–0.99; fixed effects OR = 0.62, 95% CI 0.42–0.93, for top vs. bottom category, p for heterogeneity = 0.25).

Conclusions

The limited epidemiological evidence suggests no relation between endometrial cancer in the ranges of dietary vitamin D examined, and suggests a possible inverse association for calcium from supplements. Prospective studies, ideally including plasma 25(OH) D to estimate vitamin D input from diet and sun exposure, are needed to further explore these hypotheses.

Introduction

Few dietary factors besides obesity have been consistently convincingly related to endometrial cancer risk in systematic literature review (World Cancer Research Fund and American Institute for Cancer Research, 1997, Bandera et al., 2007c).

A recently published ecological study of UV irradiation (Mohr et al., 2007) and endometrial cancer incidence supported a role for vitamin D in the etiology of this cancer (Grant, 2002, Grant and Garland, 2006). Although the vitamin D hypothesis is intriguing, ecological studies are subject to important shortcomings limiting causal inference (Mohr et al., 2007, Schwartz and Porta, 2007). For example, UV exposure may be a proxy for physical activity, which is inversely related to endometrial cancer risk (Bandera et al., 2007c).

Vitamin D and calcium are highly correlated in the diet and are metabolically interrelated (Heaney et al., 1997). Both have anti-proliferative and pro-differentiation effects in vitro (Lipkin and Newmark, 1999), and may work synergistically to reduce cancer risk (Grau et al., 2003, Lappe et al., 2007). We therefore provide the results of a systematic literature review and meta-analysis of vitamin D, calcium, and endometrial cancer risk conducted to support the 2007 WCRF/AICR Report on Food, Nutrition, Physical Activity and the Prevention of Cancer (Bandera et al., 2007c) to encourage more research in this area.

Section snippets

Methods

Our general methods followed the WCRF Specification Manual for systematic literature reviews, available online at www.wcrf.org. Further details are provided elsewhere (Bandera et al., 2007c). Interpretation of the evidence may not represent the views of WCRF and may differ from those in the 2007 WCRF/AICR report summarizing evidence related to food, nutrition, physical activity, and cancer risk.

Results

We found no intervention or cohort studies on vitamin D or calcium and endometrial cancer. As shown in Table 1, only three hospital-based case control studies (Barbone et al., 1993, Negri et al., 1996, Salazar-Martinez et al., 2005) reported on the association of dietary vitamin D and endometrial cancer risk and offered conflicting results. Meta-analyses of vitamin D and endometrial cancer were null (random-effects pooled OR = 0.85, 95% CI 0.34–2.13; fixed-effects pooled OR = 1.14 (95% CI

Discussion

Our systematic literature review of vitamin D, calcium and endometrial cancer indicates that the evidence is sparse and inconclusive. The three published case-control studies of vitamin D, which evaluated only dietary intake, found inconsistent associations with endometrial cancer. Five case-control studies evaluated the relationship between dietary and supplemental calcium and were generally inconsistent but offered some support for an inverse association with supplemental calcium. There were

Conclusions

The current evidence for a role of dietary vitamin D or calcium in endometrial carcinogenesis is too limited to draw any conclusions. The available epidemiological studies may have missed a true association due to misclassification of vitamin D status when only considering the low range from dietary sources, and potentially missing the relevant time frame of exposure. The modest inverse relationship observed between calcium supplementation and endometrial cancer may be explained by bias,

References (30)

  • E.R. Bertone-Johnson et al.

    Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer

    Cancer Epidemiol. Biomark. Prev.

    (2005)
  • E. Giovannucci et al.

    Prospective study of predictors of vitamin D status and cancer incidence and mortality in men

    J. Natl. Cancer Inst.

    (2006)
  • W.B. Grant

    An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation

    Cancer

    (2002)
  • W.B. Grant et al.

    The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates

    Anticancer Res.

    (2006)
  • M.V. Grau et al.

    Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial

    J. Natl. Cancer Inst.

    (2003)
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    Disclaimer: This work was funded in part by the World Cancer Research Fund (WCRF) and by the National Cancer Institute (NIH-K07 CA095666 to Dr. Bandera). However, interpretation of the evidence may not represent the views of WCRF or the NCI, and our conclusions may differ from those in the 2007 WCRF report summarizing evidence related to food, nutrition, physical activity, and cancer risk.

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