br Subjects with the variant alleles CT and TT
Subjects with the variant USP7/USP47 inhibitor (CT and TT) of XPC C > T (Ala499Val, rs2228000) polymorphisms reported to exhibit a 8.6% and 13.1% decrease in DNA damages induced by BPDE and gamma-radiation respectively (Zhu et al., 2008). In the present report the variant allele T for this XPC polymorphism were observed to give protection against the de-velopment of pre malignant lesions like OSMF but not oral cancer. Wang et al. also reported similar protective association of T allele with the risk of oral pre malignant lesions (Wang et al., 2007). Huang et al. reported that individuals with XPC T allele exhibited a significantly reduced risk for advanced colorectal adenoma in their case-control study and this finding was supported by a haplotype analysis (Huang et al., 2006). Similar results of the variant T alleles for XPC (Ala499Val) were also reported by Zhu et al. and Zhou et al. (Zhu et at., 2007; Zhou et al., 2006). A plasmid based NERC assay reported a probable effect of the XPC C > T polymorphism on the function of XPC protein (Lockett et al., 2005). Moreover, this polymorphism is in LD with another polymorphism located in the putative transcription factor binding site at the 5’ UTR of the XPC gene. This UTR polymorphism has been predicted to alter the function of XPC gene by
affecting its transcription and is reported to enhance the risk of SCC of lung (Lee et al., 2005).
Zhu et al. showed that BPDE-induced DNA damage was significantly higher in carrier of C allele for XPC A > C (Lys939Gln, rs2228001) polymorphism than the carrier of A allele. Similarly, subjects carrying at least one variant C allele exhibited significantly higher γ-radiation-induced DNA damage than the wild-type genotype. (Zhu et al., 2007). However, in vitro studies measuring DNA repair capacity of C allele for XCP A > C polymorphism has shown inconclusive and contradictory results (Qiao et al., 2002d). In the present study the common allele genotype AA for XPC A > C polymorphism was found to be protective for the develop-ment of oral diseases especially of oral cancer and Lichenplanus, while it increased the risk of OSMF. Such contrasting association is possibly due to the fact that Lichenplanus and OSMF are two different diseases. We have previously reported association of this polymorphism with risk of PMOL. Beside oral and pre oral cancer the C allele of XPC A > C polymorphism is also documented to enhance the risk of colorectal cancer, especially in Asian population (Peng et al., 2014).
Haplotypes constituted from the three XPC polymorphisms studied here showed that the haplotypes with T and A allele respectively from of XPC C > T and A > C polymorphisms were protective against the development of oral diseases which further strengthen our observation that the T allele and A allele for these two XPC polymorphisms give protection against the development of oral diseases.
In conclusion, the present study demonstrates association of XPC A > C (Lys939Gln, rs2228001), C > T (Ala499Val, rs2228000) and intron 9 PAT (D > I) polymorphisms with the risk for development of oral precancerous lesion as well as oral cancer. The C > T polymorphism not only modifies the risk for development of oral cancer but also influences the clinical characteristics of the same.
The authors thank Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow for providing facilities to conduct the experiments.
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