Clinical, pathological, cellular and molecular lesions caused by oral smokeless tobacco – a review

Abstract

While carcinogenicity of smokeless tobacco (ST) to humans is well established the oral lesions that precede development of cancer are less well characterized. The clinical appearances of ST-associated lesions are variable. Epidemiological studies show a strong significant association of risk with chronic daily use but population differences are noted because of various commercial products in use. Morphological features observed are some what different to oral lesions caused by smoking and oral dysplasia in ST-associated lesions is less common. Effects of ST on oral keratinocytes observed in vitro include alterations in cell proliferation, apoptosis and activation of inflammatory markers. Genetic aberrations caused by ST include activation of ras, uncommon in smokers but mutational hot spots in p53 encountered are similar to those in smokers.

Smokeless Tobacco (Shammah) in Saudi Arabia: A Review of its Pattern of Use, Prevalence, and Potential Role in Oral Cancer

“…Effects of ST on oral keratinocytes observed in vitro include alterations in cell proliferation, apoptosis and activation of inflammatory markers. Genetic aberrations caused by ST include activation of ras, uncommon in smokers but mutational hot spots in p53 encountered are similar to those in smokers (Warnakulasuriya and Ralhan, 2007). Previous studies have demonstrated that an aqueous ST extract when given in a single oral dose to experimental rats results in an superior induction of liver lipid peroxidation, hepatic DNA single strand breaks (apoptosis marker), and a marked augmentation in the urinary excretion of the lipid metabolites malondialdehyde, formaldehyde, acetaldehyde, and acetone (Bagchi et al, 1994;Bagchi, 1997;Chole et al, 2010;Ramya et al, 2011;Kurtul and Gökpınar, 2012).…”

“…ST has been associated with an increased risk for oral cancer in the southern United States (Winn et al, 1981). In a study of 1109 professional baseball players in the United States, 203 (18,3%) had oral mucosal lesions; of these affected subjects, 196 (96,6%) were current users of ST (Warnakulasuriya and Ralhan, 2007;Warnakulasuriya et al, 2010). A few studies conducted in KSA reported similar findings (See next section) (Salem et al, 1984;Hannan et al, 1986;Salem, 1989;Allard et al, 1999;Al-Balawi and Nwoku, 2002;Halboub et al, 2011).…”

“…While carcinogenicity of ST to humans is well established the oral lesions that precede development of cancer are less well characterized. The clinical appearances of ST-associated lesions are variable (Warnakulasuriya and Ralhan, 2007). The most frequently reported sites of oral cancer among shammah users in one report were tongue (33%) and oral vestibule (32%) (2); in another study, tongue (15%), floor of mouth (18%), retromolar trigone (18%), and buccal mucosa (49%).…”

“…The most frequently reported sites of oral cancer among shammah users in one report were tongue (33%) and oral vestibule (32%) (2); in another study, tongue (15%), floor of mouth (18%), retromolar trigone (18%), and buccal mucosa (49%). Morphological features observed are somewhat different to oral lesions caused by smoking and oral dysplasia in shammah-associated lesions is less common (Warnakulasuriya and Ralhan, 2007). A study included Saudi citizens from the general population, in an age range from 20 to 57, composed of males and females.…”

Loss of DLC1 is an independent prognostic factor in patients with oral squamous cell carcinoma

“…1 Oral squamous cell carcinoma is often preceded by clinically well-defined lesions such as leukoplakia, causally linked with chronic exposure of the oral mucosa to carcinogens/growth promoters in tobacco and alcohol. [2][3][4] Although DNA aneuploidy and grade of dysplasia have been used as predictors for progression of dysplasia to cancer, these are not accurate predictors for evaluating the risk of malignancy. [5][6][7][8] Furthermore, oral squamous cell carcinoma patients also show poor clinical outcome owing to loco-regional recurrence, metastasis, or development of second primary tumors, despite advances in combined multi-modality therapy.…”