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  • br Genotypes of XPC polymorphisms and risk of pre

    2022-05-10


    3.3. Genotypes of XPC polymorphisms and risk of pre malignant lesions and oral cancer
    As the study showed association of studied XPC polymorphism with the oral disease, we assessed whether they were associated with oral premalignant lesions or oral cancer and thus further stratified our cases in two groups: (i) patients with pre oral cancer lesion and (ii) patients with oral cancer. Distribution of different genotypes and Testosterone for XPC polymorphisms among the patients of pre oral cancer lesions and his-tologically confirmed oral cancer patients are documented in Table 4. The protective association of variant allele genotype (D/I and I/I) for XPC intron 9 polymorphism was documented both with pre malignant
    Table 4
    Frequency distribution of different genotypes and alleles of XPC PAT D > I, XPC C > T, XPC A > C polymorphisms among oral pre cancer (Oral submucous fibrosis + Lichenplanus, + Leukoplakia), cancer and controls.
    Genotypes Pre-oral cancer P-value Odd ratio (95% CI) Oral cancer P- value Odd ratio (95% CI) Controls
    Significant association.
    3.4. Haplotypes of XPC polymorphisms and risk of oral diseases
    Haplotyping of XPC A > C (rs2228001) C > T (rs2228000) and intron 9 PAT (D > I) (rs77907221) polymorphisms generated 8 dif-ferent haplotypes as detailed in Table 6. Compared to the A/C/D hap-lotype the frequency of A/T/D and A/T/I haplotype were significantly higher among the control population than in patients with oral diseases (Table 6) indicating a protective association of these haplotypes with the susceptibility to develop any kind of oral disease including pre malignant lesions and oral cancer. The frequencies of other haplotypes were almost similar between cases and controls. Further, the above polymorphisms of XPC were not in significant LD (D = 0.0089 for D/I and C > T; 0.0477, for D/I and A > C and 0.0411 for C > T and A > C polymorphism).
    3.5. XPC gene polymorphisms in relation to different clinical parameters of patients with oral cancer
    Distribution of genotypes for different XPC polymorphisms among different disease categories are listed in Table 7. Frequency of patients with variant allele genotypes (D/I + I/I) for XPC intron 9 PAT poly-morphism were higher (63%) among high stage (stage III + IV) diseases compared to low stage disease (sate I + II; 16%). Similarly, risk of being diagnosed with larger size tumor were significantly higher (OR = 3.5; Table 7) with D/I + I/I genotypes than D/D genotypes. Compared to D/ D genotypes, patients with D/I + I/I genotypes were also found to harbour metastatic disease at the time of diagnosis. Rest of the
    Table 5
    Frequency distribution of different genotypes and alleles of XPC PAT D > I, XPC C > T, XPC A > C polymorphisms among cases of Testosterone Oral submucous fibrosis, Lichenplanus, Leukoplakia and healthy controls.
    Genotypes Oral submucous fibrosis P- value Lichenplanus P- value Leucoplakia P- value Controls
    XPC PAT D/IGenotypes Ref 34 Ref 42 Ref 138
    Significant association.
    Table 6
    Distribution of different haplotypes of XPC A > C, C > T & PAT D > I polymorphism in Oral diseases and controls.
    SNP1 SNP2 SNP3 Cases Controls p- value Odds ratio 95% CI
    Significant association.
    genotypes for XPC A > C and C > T polymorphisms did not show any association with any clinical parameters of oral cancer (Table 7).
    4. Discussion
    Premalignant oral lesions often lead to the development of oral cancer and prevention of oral lesion could therefore reduce the in-cidence of oral cancer. This indicates that identification of susceptibility markers such as SNP for pre malignant as well as malignant oral lesion will be helpful in proper management of oral diseases. SNPs of DNA repair genes, particularly of XPC have been previously reported to alter the risk of many different cancers. However, the association of XPC polymorphisms with oral cancer and especially with pre malignant oral lesions are not well explored. In the present study we analysed the association of XPC A > C (Lys939Gln, rs2228001), C > T (Ala499Val, rs2228000) and intron 9 PAT (D > I) polymorphisms with the risk for development of pre malignant oral lesions as well as oral cancer.