Colorectal cancer is the third most common cancer and causes over 50,000 deaths a year in the US alone (1,2). People with vitamin D deficiency may have an increased risk of developing various cancers, including colorectal cancer, according to observational and preclinical studies. A large meta-analysis published in the Journal of Clinical Oncology looked at relative risk data from over 1,000,000 people and found that low vitamin D intake and low vitamin D blood levels were associated with higher risk of colorectal cancer (3).
Separate studies have shown that Vitamin D might regulate anticancer genes, and therefore, offer some protection against cancer (4). However, randomised controlled trials found that vitamin D supplementation does not improve outcomes in patients with colorectal adenomas (5).
Therefore, the question still remains of whether vitamin D deficiency can cause cancer. This question has significant economic and healthcare implications because Vitamin D deficiency affects large numbers of people in all areas of the world (6). Vitamin D is produced in the skin after exposure to UV rays in sunlight. Many people have insufficient sun exposure due to a number of factors, including: living in cold climates; spending most of their time indoors; excessive sun protection to prevent skin cancer or having dark skin.
Vitamin D deficiency can be easily treated with oral supplements. If low vitamin D levels really do cause cancer, supplementation could be a cheap and simple way to decrease cancer risk.
Genetic Markers Can Predict Vitamin D Deficiency
A new study turned to genes to answer this question. The study used biobanked samples to look at whether genetic markers of low Vitamin D levels are related to colorectal cancer risk. The researchers used six genetic markers that associate with low Vitamin D levels in GWAS studies. They first validated these genetic markers in 2,821 healthy Scottish controls and found that the markers did predict Vitamin D levels in the blood (5). They then compared data from 10,725 colorectal cancer patients and 30,794 healthy controls from Scotland, Croatia and UK Biobank participants. The researchers used Mendelian Randomisation to test whether the genetic markers for Vitamin D deficiency were causally associated with an increased risk for colorectal cancer. This kind of large scale genetic study is greatly facilitated by biobanks, which collect and securely store large numbers of biological samples and associated clinical data.
Vitamin D Deficiency is Unlikely to Cause Colorectal Cancer
The study found no direct causal association between the genetic markers for Vitamin D deficiency and the risk of colorectal cancer. There was also no association between the genetic markers for Vitamin D deficiency and other predictors of cancer risk such as age, sex, BMI, physical activity or history of smoking.
Conclusions
These results show no genetic link between vitamin D deficiency and increased risk of colorectal cancer. These data support two previous Mendelian Randomisation studies showing that low Vitamin D levels do not cause colorectal cancer. However these results are in direct contrast with the preclinical and observational studies showing that low vitamin D is associated with increased risk for a number of cancers. One explanation could be that vitamin D levels correlate with cancer risk but do not cause cancer. Large biobanking projects such as the UK Biobank and the Precision Medicine Initiative in the US may be able to help confirm this theory.
References
- Torre et al. Global cancer statistics.Cancer J Clin. 2012
- Key Statistics for Colorectal Cancer. American Cancer Society. Online (accessed 21 August 2018)
- Ma et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol. 2011
- Feldman, D et al. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014.
- He et al. Exploring causality in the association between circulating 25-hydroxyvitamin D and colorectal cancer risk: a large Mendelian randomisation study. BMC Med. 2018.
- Palacios, C and Gonzalez, L. Is Vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2015
