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Alterations in XRCC1 gene profile in pathogenesis of oral cavity cancer: A population-based study from Kamrup Urban District of Assam, India.

XRCC1 gene is an integral component of the base excision repair pathway regulating DNA repair, the genetic alterations in which has been documented to be associated with cancers of multiple etiologies. The present study aimed to evaluate the key polymorphisms in XRCC1 gene for its association with pathogenesis of oral cavity cancer (OCC) in Kamrup Urban District of Assam, India. Tissue biopsies (N = 152) clinicopathologically characterized OCCs were collected along with whole blood samples (N = 190) from healthy controls with all clinical and habitual details. A PCR-RFLP approach was used to study the XRCC1 polymorphisms, and statistical associations with pathogenesis were studied with SPSSv13.0 statistical software. The XRCC1 codon 194 polymorphism was significantly associated with the risk of OCC (odds ratio [OR] = 1.878, P = 0.048) and severity (OR = 2.221, P = 0.031). The presence of XRCC1 280 variant genotype increased the risk of OCC in exclusive smokers (OR = 3.818, P = 0.006), exclusive alcoholics (OR = 3.144, P = 0.027), and in exclusive areca nut chewers (OR = 3.055, P = 0.034). Human papilloma virus cases with any other habitual risk factor carrying XRCC1 280 genotype showed 3-fold significantly increased risk compared to controls (OR = 3.341, P = 0.022). The presence of XRCC1 codon 399 polymorphism was also found to be associated with significantly increased risk of oral cavity carcinoma (OR = 1.566, P = 0.049). Distribution of altered XRCC1 gene haplotype was higher in OCC cases. Polymorphisms in XRCC1 gene is associated with OCC pathogenesis in Kamrup Urban District, Assam, India, and is of prognostic significance. It is also suggestive of the importance of base excision repair pathway alterations in OCC pathogenesis.

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