Association between Vitamin D levels and breast cancer risk using a Mendelian randomization approach

Several studies have been done to evaluate the association of vitamin D deficiency and breast cancer risk. There is controversy in the literature about this association. Epidemiologic studies have investigated whether people with higher vitamin D intakes or higher blood levels of vitamin D have lower risks of specific cancers. The results of these studies have been inconsistent, possibly because of the challenges in carrying out such studies. Several randomized trials of vitamin D intake have been carried out, but these were designed to assess bone health or other non-cancer outcomes. Although some of these trials have yielded information on cancer incidence and mortality, the results need to be confirmed by additional research because the trials were not designed to study cancer specifically. Current evidence regarding vitamin D and breast cancer was reviewed to inform clinical practice and identify potential research directions. The evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Current evidence is sufficient to support further study of factors influencing 25(OH)D levels, associations between 25(OH)D levels and breast cancer in premenopausal and Black women, moderate dose (≤2,000 IU D3/day) supplemental vitamin D use and breast cancer incidence, and observational studies evaluating whether a threshold higher 25(OH)D level is associated with adverse clinical outcome in women with breast cancer. Before routine clinical application of any strategies targeting vitamin D status for breast cancer prevention or therapy are undertaken, the limitations of the current evidence should be considered.N