Fig. 2.

Induction of genetic and epigenetic instability due to betel quid chewing. Genetic instability includes formation of DNA adducts leading to deleterious DNA damage and promotion of chromosomal breakage. Besides, DNA mutations such as formation of novel SNP (Single Nucleotide Polymorphism), insertion-deletion mutation as well as the generation of aneuploid cells is also evident. Alterations in cell cycle pathways due to mutations and epigenetic modifications of certain cell cycle regulator genes can be observed. Epigenetic instability includes histone acetylation, methylation and promoter methylation of key regulatory genes involved in tumor suppressor defense, i.e., normal cell cycle regulation. Promotor DNA hypermethylations of tumor suppressor genes leads to the upregulation of COX-2 via NFκβ pathway. Concomitant prostaglandins production reflects the inflammation and mucosal damage, which may eventually promote the development of oral, esophageal or gastric cancer.