title: Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer.
abstract: Tobacco users with diminished ability to repair somatic mutations may be more susceptible to tobacco attributable cancers. The distribution of single nucleotide polymorphisms (SNPs) in DNA repair genes XRCC1 and XPD in 110 oral carcinoma cases, 84 leukoplakia and 110 controls belonging to the Travancore South Indian population were examined. SNPs investigated included Arg194Trp, Arg280His, and Arg399Gln of the XRCC1 gene and Lys751Gln of the XPD gene. In addition, one of the variants positions, A399G, was mapped onto the BRCT I domain model built by comparative modeling (threading). Presence of the polymorphic variant of XRCC1 codon 194 and 399 and XPD was associated with increased risk of oral cancer compared to the wild genotype. Smokers and betel quid chewers with the variant allele of XRCC1 399 codon and XPD also exhibited increased risk of oral cancer. The A399G variant position mapped onto the surface of the BRCT I domain provides a possible rationale for altered XRCC1 function. These results suggest that polymorphisms in functionally important repair genes, specifically, those that map onto the protein surface may alter protein function without significantly affecting its structure.
authors.affiliation: Department of Molecular Medicine, Regional Cancer Centre, Thiruvananthapuram 695 011, India.
authors.forename: Surya
authors.initials: S
authors.lastname: Ramachandran
authors.forename: K
authors.initials: K
authors.lastname: Ramadas
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Hariharan
authors.forename: R
authors.initials: R
authors.lastname: Rejnish Kumar
authors.forename: M
authors.initials: M
authors.lastname: Radhakrishna Pillai
mesh_terms: D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics*; D031721:Piper betle; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014030:Tobacco, Smokeless; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human