Molecular Pathogenesis of Chewable Tobacco

Abstract

In Pakistan, extensive use of several precarious chewable tobacco formulations has made oral cancer the second leading malignancy. Selection of literature was done by a survey of studies published from 1990 to 2017 mainly, from PUBMED and few from other search engines, on naswar, gutka, areca nut and betel quid, which included published reviews, original articles and other data sources on chewable tobacco, its epidemiology, pathological implications, and psychological effects. These studies have revealed that the chemicals in these formulations bind and mutate DNA of oral mucosa through down regulating cellular repair pathways and upregulating genetic networks associated with pathogenesis. Areca nut, having aercoline (the major alkaloid) causes carcinogenicity, mutagenicity, and genotoxicity of oral mucosa through increased production of growth factors and corticotrophin-releasing hormone, and genetic alteration in expression of CASP8, APAF-1, BAX, BAD, and upregulation of caspas-3. Gutka addiction leads to precancerous lesions resulting in characteristic facial abnormalities, following trismus. Naswar, in addition to oral cancer, causes adverse cardiovascular events by reducing glutathione per oxidase (GPx) and super-oxide dismutase (SOD), serum levels of HDL, whereas, increasing the ratio of cholesterol, LDL, triglycerides and LDL-C/HDL-C. Betel quid (Paan), causes psychoactivity affecting central and autonomic nervous systems leading to dependence with decreased cognition, euphoria, sweating, salivation, palpitation, heightened alertness and zest to work. Metabolically, cardio-acceleration, cortical desynchronisation of EEG, elevated plasma noradrenaline and adrenaline were found. This review highlights the corrosive effects of various most popular chewable tobacco formulations; and damage done by their cocktail of carcinogenic substances and added ingredients, leading to oropharangeal cancer.

Common Cancers in Karachi, Pakistan: 2010-2019 Cancer Data from the Dow Cancer Registry

“…17 These are kept in mouth for several hours, thus exposing the mucosa to the chemicals and thus increased chances of developing oral submucosal fibrosis and oral cancers. 18 Importantly, knowledge regarding the detrimental effects of smokeless tobacco is poor in Karachi. 19 Therefore, relevant intervention by concerned authorities can play a vital role in controlling this preventable cancer.…”

Smokeless tobacco use: its prevalence and relationships with dental symptoms, nutritional status and blood pressure among rural women in Burkina Faso

“…In addition, depending on the cultivated soils and production processes, some unusually high levels of known components and unexpected toxins have been identified in SLT leaves [9,10]. Recent international studies revealed serious health concerns related to SLT consumption, specifically oral health impairment [11,12], nutritional disorders [13], co-use of psychoactive substances, and cardiovascular disease [14][15][16]. In Burkina Faso, no previous study using a representative sample has reported the national prevalence of SLT use and its health-related consequences in rural areas, particularly among females.…”

Oral cancer via the bargain bin: The risk of oral cancer associated with a smokeless tobacco product (Naswar)

“…Nicotine causes dependence and a higher nicotine level coupled with a high pH can cause stronger cravings and more frequent and/or prolonged use of the SLT products [ 35 ], leading to a stronger exposure to the carcinogenic agents. There are also suggestions that Naswar causes local tissue trauma by erosion [ 36 ], and chronic tissue trauma is an independent risk factor for cancer [ 37 ]. The ash and lime used in the preparation of Naswar may also be contributing a high level of toxins and heavy metals to the composition, thus adding to its potential toxicity [ 14 ].…”