这项研究深入探讨了口腔癌的复杂情况，口腔癌是一个全球性问题，在亚洲国家发病率很高。我们专注于口腔鳞状细胞癌（OSCC），这主要是由食用槟榔及其衍生物引起的。 OSCC 通常由口腔粘膜下纤维化 (OSF) 等癌前病变引起。在巴基斯坦，由于各种成瘾物质（包括无烟烟草和咀嚼材料），口腔鳞癌在男性中普遍存在。 TP53 和 p21 等肿瘤抑制基因的突变在这种恶性肿瘤的发展中发挥着至关重要的作用。我们还探讨了 TUSC3 基因缺失在 OSCC 和 OSF 中的参与。在这项研究中，我们调查了 OSCC 和 OSF 患者的人口统计学、TUSC3 基因表达、缺失分析以及 TP53 和 p21 基因改变（每种情况下 50 个样本的血液和组织）有烟草衍生物使用史的人。关联分析主要通过基于 PCR 的基因分型进行。该研究的患者队列（OSCC 和 OSF）显示年龄范围广泛，从 13 岁到 65 岁（平均值 = 32.96 岁）。这两种情况在男性中更为普遍，男女比例约为 2.5:1。咀嚼习惯分析显示 OSF 和 OSCC 患者使用古特卡的频率很高。 OSCC 细胞系中的 TUSC3 表达分析表明显着下调。基因分型显示 OSF 病例中没有 TUSC3 缺失，但 OSCC 组织样本中缺失率超过 22%。分析支持 TUSC3 缺失与 OSCC 发展存在显着关联，但与 OSF 无关。 p53 外显子 4 和 p21 (rs1801270) 的多态性与 OSCC 和 OSF 显着相关，从而加剧了它们的发病机制。我们的研究结果进一步揭示了 TUSC3 缺失与过度使用烟草及相关产品之间的密切相关性，从而揭示了 OSCC 发展的遗传基础。值得注意的是，我们的研究为响应成瘾消费而导致 OSCC 和 OSF 的遗传方面提供了重要的见解槟榔、槟榔和烟草衍生物。 TUSC3 缺失与 OSCC 发展之间的显着关联，以及 TP53 和 p21 的多态性，强调了进一步研究驱动口腔癌进展的分子机制以改善诊断和治疗结果的重要性。© 2024。作者。

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.© 2024. The Author(s).