Vitamin D and prevention of breast cancer: Pooled analysis

https://doi.org/10.1016/j.jsbmb.2006.12.007Get rights and content

Abstract

Background

Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose–response relationship in individuals has not been adequately studied.

Methods

A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with 1760 individuals. Data were pooled to assess the dose–response association between serum 25(OH)D and risk of breast cancer.

Results

The medians of the pooled quintiles of serum 25(OH)D were 6, 18, 29, 37 and 48 ng/ml. Pooled odds ratios for breast cancer from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70 and 0.50 (p trend < 0.001). According to the pooled analysis, individuals with serum 25(OH)D of approximately 52 ng/ml had 50% lower risk of breast cancer than those with serum <13 ng/ml. This serum level corresponds to intake of 4000 IU/day. This exceeds the National Academy of Sciences upper limit of 2000 IU/day. A 25(OH)D level of 52 ng/ml could be maintained by intake of 2000 IU/day and, when appropriate, about 12 min/day in the sun, equivalent to oral intake of 3000 IU of Vitamin D3.

Conclusions

Intake of 2000 IU/day of Vitamin D3, and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

Section snippets

Background

A wide range of ecological studies have linked low levels of sunlight or ultraviolet B irradiance with high breast cancer rates [1], [2], [3], [4], [5], [6], and studies of markers of ultraviolet B exposure individuals have supported this association [7]. However, until recently, it was not possible to estimate the dose–response relationship. Vitamin D status is assessed by the level of 25(OH)D in the serum. This is the predominant Vitamin D metabolite in the circulation because its half life

Methods

A PUBMED search for 1966–2006 was performed by two investigators studies. The search was performed by using the terms (“Vitamin D” or “cholecalciferol” or “calcidiol” or ”calcitriol”), and (“cohort” or “case–control” or “case–cohort” or “incidence” or “occurrence” or “epidemiology” or “clinical trial”) and “human” as medical subject heading (MeSH) terms and words in the abstract, combined with the subject term “breast neoplasms”. Articles were included if they were published in medical

Results

Both studies found lower risk of breast cancer in individuals with higher levels of 25(OH)D (Fig. 1, Fig. 2). When results of these studies were pooled, the odds ratios for the pooled serum 25(OH)D studies, from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70 and 0.50 (p trend < 0.001). The dose–response relationship is shown in Fig. 3. The serum 25(OH)D concentration accounted for 90% of the variation in risk of breast cancer (p < 0.001).

Discussion

A 50% lower risk of breast cancer was associated with a serum 25(OH)D level of 50 ng/ml, compared to ≤10 ng/ml. Since 25(OH)D increases by 10 ng per 1000 IU, this serum level would correspond to intake of 4000 IU/day, assuming baseline 25(OH)D of 10 ng/ml [10]. This exceeds the current National Academy of Sciences upper limit of 2000 IU/day [20]. However, a proposal has been made to establish an upper limit of 4000 IU/day [21], [22]. Given the low background levels of 25(OH)D in US women during the

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