Role of Smoking-Mediated molecular events in the genesis of oral cancers (original) (raw)

2019, Toxicology Mechanisms and Methods

Smoking is a pernicious practice prevalent worldwide. It involves breathing of burnt-tobacco fumes/smoke which comprises of numerous chemical entities posing deleterious aftermaths in the oral cavity. Tobacco fumes carry carcinogens namely damaging chemicals like nitrosamines, polycyclic aromatic hydrocarbons, aldehydes, nicotine, phenols, carbon monoxides, radioactive elements, heavy metals ions. Oral cavity (mouth or buccal cavity), forming initial contacts with tobacco smokables, plays an essential role in the digestive system, facial determinations and speech. Smoking is a significant risk factor for oral cavity cancers. Nearly 50% of deaths from oral cavity cancer (oral cancer) attribute to smoking. This review intends to focus on the smoking mediated molecular modulations that are associated with the genesis of oral cancers. A c c e p t e d M a n u s c r i p t functional abilities are determined by the three-dimensional structure which in turn depends on the amino acids sequence and post-translational modifications (figure 1) (Crick 1970; Lin and Elowitz 2016). Smoking induces multitude aberrations in the molecular components of cells (the fundamental unit of life), ultimately disrupting the physiological homeostasis of the oral cavity (Shwetha et al. 2018). The DNA and cellular constitute of healthy oral mucosa are constant while in smoking addicts cells exhibit chromosomal, genetic and epigenetic abnormalities (Khowal et al. 2018b). During cell division, T_Sm mediated mutations are passed on to daughter cells and mutations guided fate of T_Sm exposed oral cells is followed (Lin and Elowitz 2016). This review focuses on the smoking mediated molecular modulations that are associated with the genesis of oral cancers. 2. Oral cavity cancer Cancer is a multi-factorial, complex genetic disorder. The cancer genome accumulates more and more abnormalities/mutations during tumor initiation, progression and metastasis (Bijanzadeh 2017). Though the exact genetic routes responsible for malignant transformation, are still unknown, few key attributes having concordance with cancer initiation and progression have been realized lately (Loaiza and Demaria 2016). The vital molecular characteristics favoring carcinogenesis comprises of abundant proliferative signals, circumvented growth suppressors, abstained apoptosis, abnormal cells with replicative immortality, angiogenesis and vascularisation of nascent tumors, and invasion & metastasis (Hanahan and Weinberg 2011). Cancers commonly arise in cellular/tissue microenvironments struggling from chronic built-up of oxidative and inflammatory stresses (Hanahan and Weinberg 2011). Carcinogenesis is preceded by a non-life threatening phase, with reversible pathological attributes and molecular aftermaths, termed as the pre-malignant or potentially malignant or pre-cancerous condition (Ryan and Faupel-Badger 2016); medical interventions executed during precancerous period are less stringent and show higher survival rates than the treatment strategies implemented during the cancerous period or phase of a lesion (Maza et al. 2017). The early stage diagnosis of pre-cancer and cancer lesions is crucial for determining the disease outcome; moreover, majority of cancer cases prove fatal because of diagnosis at higher/more-severe tumor grade and stage (Field and Youngson 2002). Oral cavity cancer or oral cancer is a serious life-threatening global pandemic affecting human health and lifestyle worldwide (Kampman et al. 2018). Oral cancer, a subgroup of head and neck cancers, has shown alarming prevalence globally, affecting both more developed and less developed countries. More than 90 percent of oral A c c e p t e d M a n u s c r i p t cancer cases are diagnosed as oral squamous cell carcinoma (OSCC) which are malignant lesions arising from the epithelial lining of the oral mucosa (Cameron Goertzen et al. 2018). OSCC lesions are comprised of abnormal cells showing non-regulated or uncontrolled cell divisions; the tissue surrounding cancerous loci constitutes tumor microenvironment that plays an important role in cancer sustenance, progression and immune system evasion (Nieh 2017). The oral pre-cancer (pre-malignant) conditions are major risk factors for OSCC. The oral pre-cancer conditions are indicative of epigenetic and genetic abnormalities which, in comparison to the normal/healthy physiology, pre-disposes the lesion for advancement towards malignant or cancer associated epigenetic and genetic abnormalities. The commonly diagnosed oral pre-cancer conditions include leukoplakia, erythroplakia, erythroleukoplakia and oral lichen planus (Yardimci et al. 2014; Thomson 2015). Leukoplakia is thick, white colored patch appearing in the diseased oral mucosa. Erythroplakia and erythroleukoplakia are conditions where red and red-white (mosaic) colored patches are seen respectively within the unhealthy oral cavity. Oral lichen planus, the oral pre-cancer chronic inflammatory disorder, results in bilateral white striations or plaques within the oral cavity (Deshpande 2017). Erythroplakia lesions have a strong probability of malignant transformations (Speight et al. 2017). The main etiological factors associated with oral carcinogenesis include chronic habits for the intake of tobacco, areca nut and alcoholic products (alone or in combinations) (Kumar et al. 2016; Yenugadhati et al. 2018). By various epidemiological studies, tobacco (smokable or chewable) is the primary etiology for oral cancer incidences