ReviewVitamin D and calcium intake in relation to risk of endometrial cancer: A systematic review of the literature☆
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,
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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.