RESUMO
Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor (TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with NcoI and HinfI then visualized. We did not find any difference between genotype frequencies between controls and patients (p > 0.05) in rs4986790. But a significant difference between control group and patients with lung cancer as for genotype frequencies (χ (2) = 4.19, p = 0.041) in rs4986791 variants was found. Our data indicate that any correlation was not found between rs4986790 polymorphism and lung cancer, while a correlation between rs4986791 and lung cancer has been determined and found to be associated with lung cancer risk.
Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 4 Toll-Like/genética , Adulto , Idoso , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/induzido quimicamente , Polimorfismo de Fragmento de Restrição , Fumaça/efeitos adversos , TurquiaRESUMO
BACKGROUND AND AIM: NOD1/CARD4 and NOD2/CARD15 are members of the Nod-like receptor (NLR) family, and they contain a caspase recruitment domain (CARD). NLRs are located in the cytosol where they bind bacterial and viral ligands and play a key role in the innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. NLR gene polymorphisms may shift the balance between pro- and anti-inflammatory cytokines and modulate the risk of infection, chronic inflammation, and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may also be associated with altered risks for many cancer types. The aim of our study was to evaluate the potential associations between lung cancer and NOD1/CARD4 and NOD2/CARD15 polymorphisms. METHOD: The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment-length polymorphism analysis (PCR-RFLP) in 260 subjects (lung cancer patients: n = 160; healthy controls: n = 100) of Turkish origin. PCR products were digested with AvaI for rs5743336 and ApaI for rs2066847 and then visualized. RESULTS: Comparisons of the genotypes between control and lung cancer patients were performed by Chi-square tests. We found a significant difference in the genotypic distribution of the rs5743336 variant of NOD1/CARD4 between lung cancer patients and controls (p = 0.010, χ (2) = 9.220). However, we did not identify any statistically significant difference for the p.Leu1007fsX1008 (rs2066847) genotype of NOD2/CARD15 between groups (p > 0.05). CONCLUSION: According to our data, the rs5743336 variant of the NOD1/CARD4 gene may influence the diagnosis and treatment of lung cancer, whereas the rs2066847 variant of the NOD2/CARD15 gene is not associated with lung cancer risk in the Turkish population.
Assuntos
Neoplasias Pulmonares/genética , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD2/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença/genética , Variação Genética , Genótipo , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/genética , Turquia/epidemiologiaRESUMO
AIM: To determine the incidences of copy number aberrations of receptor kinases and their relations in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: The prevalence of genomic copy number aberrations of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/topoisomerase IIa (TOP2A), centrosome-associated kinase aurora A (AURK A), centrosome-associated kinase aurora B (AURK B), and mesenchymal-epithelial transition factor (MET) genes and polysomies of related chromosomes were analyzed by fluorescent in situ hybridization (FISH) in tumor samples from 35 patients with gastric cancer. RESULTS: There were 28.6%, 65.7%, 20.0%, 17.1%, 60.0%, and 45.7% cases considered FISH-positive for EGFR, MET, HER2, TOP2A, AURK A, and AURK B genes, respectively. Statistically significant associations were determined in detection of amplifications of 1) EGFR gene with chromosome 7 polysomy, 2) MET gene in nonpolysomic chromosome 7 nuclei, 3) HER2/TOP2A genes in nonpolysomic chromosome 17 nuclei, 4) coamplification of HER2/TOP2A in poorly differentiated carcinomas, and 5) AURK A gene in nonpolysomic chromosome 20 nuclei. Most of the aberrations were predominantly seen in poorly differentiated tumors, but a high rate of the amplified MET gene was also detected in moderately differentiated carcinomas. CONCLUSION: Chromosome 7 polysomy may be responsible for EGFR gene amplifications, and we concluded that MET and AURK A genes amplifications were commonly seen aberrations in gastric adenocarcinomas and may offer information about disease progression and administration of individualized treatment for gastric cancer patients.
