Esophageal cancer is a relatively rare form of cancer, but some areas of the world have a markedly higher incidence than others: such as Belgium, China, Iran, Iceland, India, Japan, and the United Kingdom. The American Cancer Society estimates that just over 15 thousand cases of esophageal cancer are diagnosed in the United States every year.
In the United States, squamous cell carcinoma of the esophagus usually affects African Americans. The incidence of esophageal adenocarcinoma has been rising relatively rapidly over the last four decades. Humans cannot be evolving quickly enough for genetics to explain this rapid change. Instead, this indicates that environmental or behavioral factors have important roles in the etiology of the cancer. Such general evidence might make one ask, does vitamin D have a role?
Recently, Dr Joel Rubenstein of the University of Michigan Medical School wrote an editorial opining that while the vitamin D hypothesis is attractive, vitamin D should not be used to prevent esophageal cancer.
He pointed out that an ecological analysis found that counties in the United States with lower UVR exposure had greater incidences and mortality of esophageal cancer. However, ecological analyses are prone to biases called the “ecological fallacy,” because individual level data may differ from the population level data.
An example was the finding that suicide rates were more common in areas of Prussia that had higher proportions of Protestants. This in turn was interpreted as supporting the hypothesis that Catholicism prevents suicide. However, it may have been that all of the suicides in the heavily Protestant areas were committed by Catholics, and so the conclusion that Protestantism is associated with suicide would not be true, an example of the “ecological fallacy.”
A study in the same edition of the journal used residential location to examine the association between exposure to UV radiation and the frequency of cancer of the esophagus, finding a substantial inverse association between mean daily UVR exposure and adenocarcinomas of the esophagus (OR = 0.66).
In contrast to an ecological study, the study reported by Tran et al. is not an ecological analysis, as the data on both the outcomes and the exposures were at the individual, rather than the population level. However, says Dr Rubenstein, there may have been measurement error.
Dr Rubenstein concludes,
“There is no evidence to support the use of (vitamin D) supplementation. The negative association with UVR exposure (found by Tran et al.) may be due to unmeasured confounders. Perhaps there are other environmental factors related to UVR exposure that explain the association (such as soil fungi, toxins from local flora, availability of micronutrients in locally grown produce, fall-out from twentieth century nuclear weapons testing, etc.). Despite observational data suggesting protective effects, in most trials to date of vitamin or micronutrient supplementation for prevention of a number of different types of cancer, there has been no decrease in incidence or mortality, and in fact some have reported worse outcomes in the group randomized to supplementation.”
He is right; fallout from nuclear testing notwithstanding, the evidence does not support the use of vitamin D supplements to prevent esophageal cancer. However, the evidence is overwhelming that vitamin D supplements prevent vitamin D deficiency and such deficiency puts one at risk for a breathtaking array of diseases, one of which may or may not be esophageal cancer.