RESUMO
Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Consenso , Receptores ErbB/genética , Europa (Continente) , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Mutação , Patologia Molecular/métodos , Equipe de Assistência ao Paciente , Guias de Prática Clínica como Assunto , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Receptores Proteína Tirosina Quinases/genética , Proteínas ras/genéticaRESUMO
Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).
Assuntos
DNA Glicosilases/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Primers do DNA/genética , Feminino , Genótipo , Humanos , Masculino , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Fatores Sexuais , Eslováquia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVE: The aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population. MATERIAL AND METHODS: The study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. We determined the genotype distribution of all these genes and their combinations. The association between specific genotypes and the development of lung cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: We found that the GSTM1 null genotype (OR=1.6; 95% CI=1.03-2.4; chi(2)=4.08, and P=0.04) was associated with elevated risk. A significant correlation also was found for the combined genotypes of GSTM1 null and GSTP1 Ile/Val and Val/Val (OR=2.01; 95% CI=1.1-6.1; chi(2)=3.6, and P=0.02) and GSTM1 null and GSTT1 positive (OR=2.00; 95% CI=1.2-3.2; chi(2)=7.3, and P=0.006). CONCLUSIONS: We conclude that the genotype of metabolizing enzymes and allelic combinations underscore the risk for lung cancer. Individual risk assessment may be further improved by increasing the number of polymorphisms studied and combining them with the traditional epidemiological risk factor.
Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Genótipo , Humanos , Modelos Logísticos , EslováquiaRESUMO
The aim of the study was to test the diagnostic value of serum tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were included in this study: 56 with SQCLC-Group I, 25 with other types of lung cancer-Group II, 10 with benign respiratory tract diseases-Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - > 16), in Group II: 3.58 (1.72 - > 16), in Group III: 2.05 (0.99-3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (0.76 - > 20), in Group II: 3.32 (1.17 - > 20), in Group III: 3.09 (1.84-6.37). There was a highly significant difference between the levels of CYFRA 21-1 in Group I and III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.90, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this setting.