Why only areca nut chewing cannot cause oral submucous fibrosis?

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral cavity. Most of the affected people are betel quid chewers. Although, betel quid is consumed in various forms, only areca nut chewing habit has become very rare. We came across 34 such cases with 32 showing no evidence of OSF. Therefore, we hypothesize that only areca nut chewing cannot cause OSF and presence of other factors like slaked lime and inflammation is necessary. Keeping in mind the composition of areca nut, hypothesis is comprehensively discussed at molecular level in the present paper with special emphasis on the role of TGF-beta and lysyl oxidase enzyme in OSF. If investigated in the suggested direction, it might provide an important clue about the pathogenesis of OSF and thus can help in the future development of treatment strategies.