Vitamin D and Colorectal Cancer
The vitamin D response element plays a direct role in regulating gene expression, a potential mechanism to explain how vitamin D is involved with malignancy.
Over the past decade, there has been significant research evaluating the role of vitamin D in relation to a multitude of malignancies including breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, melanoma, and colorectal cancer (CRC). The exact role that vitamin D plays in the pathogenesis and treatment of CRC remains to be fully understood, however, it is important to be familiar with some of the hypotheses and subsequent data to better inform patients of the potential risk and benefits of vitamin D supplements.
Calcitriol, also known as 1,25-(OH)2D3, is the most active form of vitamin D. It is involved in the regulation of calcium and phosphate levels as well as gene expression.1 The form that is typically measured in blood is 25(OH)D. Once calcitriol binds to its receptor, it will form a complex with the retinoid X receptor (RXR), which will in turn bind the vitamin D response element (VDRE).1 VDRE plays a direct role in regulating gene expression, which is one of the potential mechanisms that explains how vitamin D is involved with malignancy. Vitamin D can induce expression of cyclin-dependent kinase inhibitors (CDKi) and inhibit expression of cyclin D-1.1
Vitamin D may also have anti-inflammatory effects that lend to its potential anticancer properties.1,2 In animal models, vitamin D has been shown to reduce proinflammatory cytokines such as interleukin 1 and tumor necrosis factor (TNF) alpha.3 Patients with inflammatory bowel diseases, such as ulcerative colitis and Crohn disease, are at an increased risk of developing CRC. This increased risk of CRC is undoubtedly multifactorial; however, the role of vitamin D should not be overlooked, especially because many of these patients are deficient. Therefore, routine monitoring of vitamin D levels in patients with inflammatory bowel disease is often recommended.
There are have been many clinical studies evaluating the role of vitamin D and its levels in the setting of CRC prevention. A meta-analysis conducted by Chung and colleagues demonstrated a 6% reduced risk of colorectal cancer for every 10 nmol/L increase in 25-OH vitamin D levels in the blood.4 Interestingly, there was no statistically significant effect seen in patients with breast and prostate cancer.
A case control study from the Nurses' Health Study found an inverse linear association between plasma 25(OH)D levels and CRC risk: the higher the 25(OH)D levels, the lower the CRC risk.5 Interestingly, this association was not found in all women or locations of CRCs. This association was strongest in women older than 60 years. In addition, cancers in the proximal colon did not show a statistically significant association with vitamin D (P = .81), but the cancers in the distal colon and rectum did (P = .02).