Vitamin D and esophageal cancer

Abstract

Esophageal cancer can present as two histological subtypes of esophageal cancer, adenocarcinoma or squamous cell carcinoma. The vast majority, if not all, esophageal adenocarcinomas arise from Barrett’s esophagus. Similarly, squamous dysplasia carries an elevated risk of progression to esophageal squamous cell carcinoma. Both cancer types have extremely poor survival rates, and therefore there is an acute need to identify modifiable risk factors that may help to prevent their development. Despite the mechanistic and ecological support for a general anti-carcinogenic role of vitamin D, studies in relation to esophageal cancer have illustrated conflicting results. Studies of vitamin D intake have been inversely associated with squamous cell carcinoma risk and directly associated with adenocarcinoma risk in European studies, while no significant associations were observed in an American case–control study. Contradictory to this, evidence from high quality prospective cohorts have illustrated that low levels of circulating vitamin D are associated with a reduced risk of esophageal squamous cell carcinoma, particularly in Asian populations. Small studies of vitamin D related genetic variants have failed to detect an association with the risk of either histological subtype of esophageal cancer. Laboratory investigations do suggest, however, that vitamin D receptor expression is more apparent in Barrett’s esophagus and esophageal adenocarcinoma tissue, and therefore are more likely to interact with vitamin D intake or status to impact on outcomes compared with squamous cell carcinomas. Whether these are positive or negative influences on development or survival remains unclear. Further work is clearly warranted in this area to fully understand the mechanisms involved and to clarify the conflicting evidence to date.