The mystery of male dominance in oesophageal cancer and the potential protective role of oestrogen

Oesophageal cancer is the sixth most common form of cancer death globally with almost 400,000 deaths annually. More than 90% of all cases are either adenocarcinomas (OAC) or squamous-cell carcinomas (OSCC). There is a strong male predominance with up to 8 and 3 men for every woman affected with OAC and OSCC, respectively. It has been hypothesised that sex hormonal factors may play a role in the development of oesophageal cancer or more specifically that oestrogen prevents such development. This article reviews the available literature on this topic. Basic science studies suggest an inhibitory effect of oestrogen in the growth of oesophageal cancer cells, and a possible mechanism of any oestrogen protection might be mediated through oestrogen receptors. But from the few epidemiological studies in which the hypothesis of oestrogen protection has been tested, no firm conclusions can yet be drawn of the role of oestrogen in human oesophageal cancer aetiology. More evidence from valid and large human studies is needed before any conclusions can be drawn.