TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan

• Published in: BMC oral health Vol. 24; no. 1; pp. 780 - 11
• Main Authors: Zaidi, Syed Aqib Ali, Chughtai, Nadia, Abbassi, Zubair Ahmed, Alam, Jehan, Malick, Tuba Shakil, Salim, Asmat, Saleem, Saima
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11-07-2024; BioMed Central; BMC
• Subjects: Adolescent; Adult; Aged; Analysis; Antibodies; Areca - adverse effects; Association analysis; Carcinoma, Squamous Cell - genetics; Care and treatment; Cell culture; Cell cycle; Cell death; Clonal deletion; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-dependent kinases; Diagnosis; DNA damage; DNA repair; Early diagnostic marker; Female; Fibrosis; Gene Deletion; Gene expression; Genes; Genetic analysis; Genetic aspects; Genetic testing; Genotyping; Health aspects; Humans; Kinases; Male; Malignancy; Medical diagnosis; Membrane Proteins - genetics; Middle Aged; Molecular modelling; Mouth cancer; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Mutation; Nuts; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Oral squamous cell carcinoma (OSCC); Oral Submucous Fibrosis (OSF); Oral Submucous Fibrosis - genetics; p21; p53 Protein; Pakistan; Proteins; Sex Factors; Squamous cell carcinoma; Tobacco; Tobacco chewing; Tobacco, Smokeless - adverse effects; TP53; Tumor proteins; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins - genetics; TUSC3; Young Adult; Pakistan; New Zealand; Japan; Oral Submucous Fibrosis (OSF); Oral squamous cell carcinoma (OSCC); TUSC3; TP53; p21; Early diagnostic marker
• ISSN: 1472-6831; 1472-6831
• DOI: 10.1186/s12903-024-04501-5

This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.
In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.
The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.
Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.