High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals

Abstract

In this study from Denmark, we investigate whether vitamin D status, usually measured by 25‐hydroxyvitamin D in blood samples, is associated with development of non‐melanoma skin cancer (NMSC). Previously, it has proven difficult to answer this particular question. If you simply divide everyone into two groups, i.e. those with a high and those with low measured 25‐hydroxyvitamin D, a higher incidence rate of NMSC would be observed in the group with high 25‐hydroxyvitamin D. However, this simple observation is susceptible to misinterpretation, e.g. sunlight's UV radiation causes damage to the skin that starts the development of skin cancer, as well as inducing vitamin D synthesis in the skin (i.e. helping the body to create vitamin D). On average, people who have higher high 25‐hydroxyvitamin D levels will therefore also have been exposed to more sunlight and UV radiation and be at higher risk of developing skin cancer. For this reason, we could observe a potentially false association between 25‐hydroxyvitamin D and cancer if we base our conclusions on just raw data alone. In this study, we used a method called Mendelian randomisation that is not susceptible to these potential errors, and we found that genetic variants affecting vitamin D neither increase nor decrease the risk of getting skin cancer. The implications of this study are that the association of 25‐hydroxyvitamin D with skin cancer cannot be taken at face value and similar studies are required for other types of cancer.