Vitamin D and breast cancer incidence: a meta-analysis.

Abstract #3101 Several genetic, hormonal, and environmental factors are implicated in the etiology of breast cancer. Vitamin D deficiency has been implicated in the pathogenesis as well as prognosis of breast cancer. Latitudinal variations of the prevalence of breast cancer suggest a benefit of increasing sunshine and resultant higher vitamin D levels. Several case-control, cohort and ecological studies suggest an increased risk of breast cancer in association with low Vitamin D intake/levels. Such association was not seen consistently. We conducted a series of meta-analyses to further assess the effect of serum Vitamin D levels on the risk of breast cancer.
 Methods: A literature search using PubMed (1950 to 2008) and cross references yielded 227 articles. We only included studies with available data on vitamin D serum levels, oral intake as well as calculated relative risk or odds ratio for breast cancer. Of these ,3 case-control studies providing details on dietary intake, 4 case-control studies of vitamin D levels, 4 studies of Vitamin D1,25 levels and 6 cohort studies of daily vitamin D intake were included in the analysis. We combined data in each category using fixed and random effect model to assess overall benefit and the dose response to vitamin D intake /levels.
 Results: In case-control studies, the odds ratios for breast cancer progressively decreased (0.94, 0.89, 0.85, 0.80, and 0.76) with increasing serum vitamin D 25 levels. This was not statistically significant ( p =.336). Increasing oral vitamin D intake did not influence the occurrence of breast cancer as the odds ratio remained unchanged, with a p of .35. In cohort studies, increasing vitamin D intake was associated with progressive reduction in breast cancer risk (.99, .98, .97, .96, .95, .94, .93) with a p of .033. With increasing vitamin D 1,25 serum levels the odds ratios of breast cancer paradoxically increased. This was not statistically significant ( p =.2).
 Limitations: Single measurements of serum levels do not account for variations due to seasonal and other factors. Long term temporal variations of vitamin D levels may be more reflective of its role in carcinogenesis through gene transduction, apoptosis and antiproliferative effect. Vitamin D intake may not directly correlate with serum levels as these studies did not assess concurrent sun exposure or absorption issues. Variable techniques were used to measure vitamin D levels which may influence the study results.
 Conclusion: This analysis did not demonstrate a conclusive clinical and statistically significant protective effect of Vitamin D on breast cancer risk. Case-control studies assessing the effect of oral intake of vitamin D or serum levels showed no statistically significant benefit. In cohort studies of vitamin D intake, a statistically significant, albeit small, trend for protection with increasing intake of Vitamin D was noted.
 Considering the limitations of these studies and the potential benefits of oral vitamin D, we suggest assessing the benefits of Vitamin D in a longitudinal model prior to recommending higher intake of Vitamin D for cancer prevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3101.