Akademik Veri Yönetim Sistemi
Pathology, research and practice, cilt.238, ss.154085, 2022 (SCI-Expanded)
Tumor Necrosis Factor-Alpha (TNF-α) is a proinflammatory cytokine that plays a role in inflammation, which is one of the hallmarks of cancer, and its polymorphic variants have been associated with disease risk in many cancers in the literature. This study aimed to investigate four different polymorphic variants in the promoter region of the TNF-α gene and to determine the association between these variants and disease risk and clinical parameters. In addition, TNF-α promoter methylation and differential expression status were investigated in our study. We purposed to investigate the genetic and epigenetic alterations of the TNF-α gene in larynx cancer (LC).
After isolation of DNA/RNA from whole blood and tumor or normal tissue, polymorphic variant alleles, expression, and methylation levels were analyzed by RFLP, semiquantitative RT-PCR, and restriction enzyme digestion. TNF-α expression and methylation levels were calculated using BIO1D software. The frequencies of the variants c.–238 G>A (rs361525), c.–857 C>T (rs1799724), c.–863 C>A (rs1800630), and c.–1031 T > C (rs1799964) in the promoter region of TNF-α in LC Turkish patients and healthy individuals were examined using the De-Finetti case-control program. Haplotype frequencies and linkage disequilibrium were analyzed using the SNPStats program.
Polymorphism genotype frequency showed that the frequency of genotype − 1031 TC was significantly lower in patients than in healthy individuals [TT vs TC: OR (%95CI) = 7.00 (1.75–27.93), p = 0.003, χ2 = 8.76]. The heterozygous variant of − 857 was associated with recurrence [T vs G: OR (%95CI) = 0.15 (0.02–0.95), p = 0.02, χ2 = 4.86]. For c.–238 G>A, c.–857 C>T, and c.–863 C>A, there is no statistically significant difference between the patient and healthy group in terms of disease risk. A significant association was found between c.–1031 T > C and disease risk of LC. Decreased expression was detected in 46% (23/50) and increased expression in 54% (27/50) of tumor tissue compared to the matched normal tissue of patients. Methylation-related loss of expression was detected in 53.3% (16/30) of patients.
Our study is the first to investigate four different polymorphic regions of the TNF-α promoter region and the expression/methylation status of TNF-α in the same LC patient and healthy cohort. According to our results, the − 1031 TC variant was reported to be significantly associated with a reduced risk of LC. In addition, the TNF-α variant − 857 CT suggests that it may be a potential biomarker for predicting the recurrence of LC. An association between its variant and methylation-based expression status was observed.
Tumor Necrosis Factor-Alpha (TNF-α) is a proinflammatory cytokine that plays a role in inflammation, which is one of the hallmarks of cancer, and its polymorphic variants have been associated with disease risk in many cancers in the literature. This study aimed to investigate four different polymorphic variants in the promoter region of the TNF-α gene and to determine the association between these variants and disease risk and clinical parameters. In addition, TNF-α promoter methylation and differential expression status were investigated in our study. We purposed to investigate the genetic and epigenetic alterations of the TNF-α gene in larynx cancer (LC).
After isolation of DNA/RNA from whole blood and tumor or normal tissue, polymorphic variant alleles, expression, and methylation levels were analyzed by RFLP, semiquantitative RT-PCR, and restriction enzyme digestion. TNF-α expression and methylation levels were calculated using BIO1D software. The frequencies of the variants c.–238 G>A (rs361525), c.–857 C>T (rs1799724), c.–863 C>A (rs1800630), and c.–1031 T > C (rs1799964) in the promoter region of TNF-α in LC Turkish patients and healthy individuals were examined using the De-Finetti case-control program. Haplotype frequencies and linkage disequilibrium were analyzed using the SNPStats program.
Polymorphism genotype frequency showed that the frequency of genotype − 1031 TC was significantly lower in patients than in healthy individuals [TT vs TC: OR (%95CI) = 7.00 (1.75–27.93), p = 0.003, χ2 = 8.76]. The heterozygous variant of − 857 was associated with recurrence [T vs G: OR (%95CI) = 0.15 (0.02–0.95), p = 0.02, χ2 = 4.86]. For c.–238 G>A, c.–857 C>T, and c.–863 C>A, there is no statistically significant difference between the patient and healthy group in terms of disease risk. A significant association was found between c.–1031 T > C and disease risk of LC. Decreased expression was detected in 46% (23/50) and increased expression in 54% (27/50) of tumor tissue compared to the matched normal tissue of patients. Methylation-related loss of expression was detected in 53.3% (16/30) of patients.
Our study is the first to investigate four different polymorphic regions of the TNF-α promoter region and the expression/methylation status of TNF-α in the same LC patient and healthy cohort. According to our results, the − 1031 TC variant was reported to be significantly associated with a reduced risk of LC. In addition, the TNF-α variant − 857 CT suggests that it may be a potential biomarker for predicting the recurrence of LC. An association between its variant and methylation-based expression status was observed.