Molecular Mechanisms of Preventable Causes of Oral Cancer and Precancer Through Polymorphism in DNA Base Excision Repair Genes in Patients with Tobacco Products Habits

通过DNA碱基切除修复基因多态性在有吸烟习惯的患者中预防口腔癌和癌前病变的分子机制

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Abstract

INTRODUCTION: The 'progression model' of oral carcinogenesis emphasizes that initial irreversible genotypic damage produces tissue disorganization and dysmaturation which, if allowed to progress, leads invariably towards invasive oral squamous cell carcinoma. Recognition of these genotypic changes is fundamental for a successful management strategy. Genetic studies have confirmed the role of pro-carcinogens present in tobacco and alcohol contributing to DNA damage and genotoxicity. Many molecular epidemiological studies have evaluated the association of head and neck cancer with polymorphisms in DNA repair genes. Our study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of DNA repair genes OGG1 Ser326Cys, APE1-Asp148Glu, XRCC1- Arg194Trp, XRCC1-Arg280His, XRCC1-Arg399Gln, ADPRT-V762A, APEX1-D148E, LIG3-R780H, MUTYH-Tyr165Cys and the risk of oral squamous cell carcinoma and oral precancerous lesions. MATERIALS AND METHOD: Our study included two patient groups. Group I (n = 58) included patients with leukoplakia, oral submucous fibrosis and biopsy-proven oral squamous cell carcinoma. Group II (n = 58) included patients who had no clinically detectable lesions. Patients in both groups had tobacco chewing and smoking history. Blood samples were collected, and gene polymorphisms were identified using PCR-RFLP technique. RESULTS AND DISCUSSION: Our study results revealed a statistically significant association between gene polymorphisms OGG1-Ser326Cys (p = 0.008), XRCC1-Arg194Trp (p = 0.009), XRCC1-Arg399Gln (p < 0.001), APEX1-Asp148Glu (p < 0.001) and the occurrence of leukoplakia, OSMF and OSCC.

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