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    Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer
    (Elsevier, 2006) Demokan, Semra; Süoğlu, Yusufhan; Demir, Deniz; Gözeler, Mustafa; Dalay, Nejat; Demir, Deniz
    Background Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer. Methods Microsatellite instability and promoter methylation were investigated by PCR, denaturing-polyacrylamide gel electrophoresis and digestion with methylation-specific restriction enzymes. Results Microsatellite instability was observed in 41% of the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the patients, respectively. BAT25 and BAT26 instability were associated with age and histopathology, respectively. Methylation frequency of the hMLH1 gene promoter was significantly higher in patients displaying a high level of microsatellite instability. Instability at the BAT 26 and D2S123 loci were associated with the MSI-high status. Conclusions Our results indicate that microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.
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    N-acetyltransferase 1 and 2 gene sequence variants and risk of head and neck cancer
    (Springerlink, 2010) Demokan, Semra; Süoğlu, Yusufhan; Gözeler, Mustafa; Demir, Deniz; Dalay, Nejat; Demir, Deniz
    Polymorphisms that alter the function of genes involved in the activation or detoxification of carcinogenic compounds can influence an individuals risk of developing cancer. Polymorphic changes modulating the acetylation capacity of the N-acetyltransferase (NAT) genes have been implicated in the risk of developing cancer. In this study the role of genetically determined individual NAT1 and NAT2 genotypes, haplotypes and haplotype combinations in the predisposition to head and neck cancer was investigated. Polymorphic regions of the NAT1 and NAT2 genes were analyzed in patients with head and neck cancer and healthy individuals by polymerase chain reaction-restriction fragment length polymorphism. Distribution of the genotypes, allele frequencies, diplotypes and haplotypes and correlation with clinical characteristics were evaluated. No association was observed between the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and NAT2*6 genotypes and risk of head and neck cancer. The NAT2*7 slow genotype was associated with reduced risk of disease. A significant association was observed between the fast acetylator NAT2*4/NAT1*10 diplotype and risk of head and neck cancer. Combined haplotypes harboring the T1088A and C1095A variants characterizing the NAT1*10 allele were associated with increased risk. Our results suggest that NAT1 and NAT2 gene combinations may influence the risk of developing head and neck cancer.
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    Polymorphisms of the XRCC1 DNA repair gene in head and neck cancer
    (Arányi Lajos Foundation, 2005) Demokan, Semra; Demir, Deniz; Süoğlu, Yusufhan; Kıyak, Erkan; Akar, Uğur; Dalay, Nejat; Demir, Deniz
    Inherited polymorphisms in the genes controlling the cell cycle or functioning in the DNA repair mechanisms may impair their function and contribute to genetic susceptibility. Abnormalities in the DNA repair have been reported in head and neck cancer. The XRCC1 gene functions in singlestrand break and base excision repair processes. In this study, two polymorphisms of the XRCC1 gene, Arg194Trp and Arg399Gln were investigated in 95 patients with head and neck carcinoma. The polymorphic regions were amplified by PCR followed by digestion with methylation-specific restriction enzymes, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and association with cancer risk or clinical parameters was investigated. No association was observed between the genotypes and head and neck cancer for either polymorphism. Distribution of the alleles did not significantly differ between the patients and the control group. A significant association was only found for the Trp194 allele among the smoking individuals. Our data indicate that the Arg194Trp and Arg399Gln polymorphisms do not confer a significant risk for head and neck carcinogenesis.