Role of drinking water copper in pathogenesis of oral submucous fibrosis: a prospective case control study

Although oral submucous fibrosis (OSMF) is thought to be multifactorial in origin, the chewing of areca nut is thought to be the main cause. Alkaloids and tannins in areca nut are responsible for fibrosis, but recent evidence has suggested that copper ions are also an important mediator, and in a small pilot study we recently found that OSMF was significantly associated with a raised concentration of copper in drinking water. We have further investigated this association in a heterogeneous population in Hyderabad-Karnataka, India, a region with a high incidence of the condition. We evaluated 3 groups, each of 100 patients: those with OSMF who chewed gutkha, those who chewed gutkha but did not have OSMF, and healthy controls who did not chew gutkha. The difference between the groups in the mean concentration of copper in water measured by atomic absorption spectrometry was significant (p<0.001). There were also significant differences between the groups in mean concentrations of serum copper, salivary copper, and ceruloplasmin (p<0.001). Our results confirm that copper in drinking water contributes to the pathogenesis of OSMF, but ingestion of copper is unlikely to be the sole cause.