Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome in advanced nonsmall cell lung cancer patients.

BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). RESULTS: The patients with TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser), GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1 polymorphic genes that we have previously genotyped in the same patients (Ada et al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016). CONCLUSION: These results show that combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival in NSCLC patients.

Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolising CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.390-3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, 95 % CI 1.54-7.41; p=0.002). Further studies with larger samples are needed to verify these findings.

Association between glutathione S-transferase omega 1 A140D polymorphism in the Turkish population and susceptibility to non-small cell lung cancer.

Recent years have seen a growing evidence of ethnic differences in the frequency of glutathione S-transferase omega 1 (GSTO1) A140D gene polymorphism, which is associated with various cancers such as breast and liver. Until now however, no association has been investigated between the GSTO1 A140D polymorphism and lung cancer. The aim of our study was to see if there was one in the Turkish population. To do that, we identified GSTO1 A140D polymorphism in 214 unrelated healthy individuals and 172 patients with non-small cell lung cancer (NSCLC) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of A/A (wild type), A/D (heterozygous mutant), and D/D (homozygous mutant) GSTO1 A140D genotypes in healthy subjects were 48%, 41%, and 11%, respectively. In NSCLC patients they were 48%, 45%, and 7%, respectively. We found no significant association between the GSTO1 A140D gene polymorphism and NSCLC or its histological subtypes, namely squamous cell carcinoma or adenocarcinoma. Furthermore, this polymorphism did not correlate with smoking. Our study is the first to show that the frequency of GSTO1 A140D gene polymorphism in the Turkish population is similar to other Caucasian populations and that this polymorphism is not associated with susceptibility to NSCLC.

Association between GSTM1, GSTT1, and GSTP1 polymorphisms and lung cancer risk in a Turkish population.

Several studies focused on investigating genetic polymorphisms in order to estimate genetic contribution to lung cancer often showed conflicting results. In this study, we investigated the role of GSTM1, GSTT1, GSTP1 exon 5 and exon 6 polymorphisms on developing lung cancer and histological subtypes in 213 lung cancer patients and 231 controls. GSTM1 null, GSTT1 null, and GSTP1 exon 5 variant genotypes did not show a significant risk for developing lung cancer overall. Significant association was noted between GSTP1 exon 6 variant genotypes and overall lung cancer risk (OR 2.17, 95% CI 1.25-3.78; P = 0.006). These results show that GSTP1 exon 6 polymorphism might be an important factor in determining lung cancer susceptibility in a Turkish population.

Expression of CD44 and MMP-2: possible association with histopathological features of pleuro-pulmonary solitary fibrous tumors.

OBJECTIVE: Recent studies have shown that tumor cell adhesion molecules CD44 and matrix metalloproteinases (MMP-2) are expressed strongly in many tumors and associated closely with invasion and metastasis of these tumors. Although solitary fibrous tumors (SFT) have a good prognosis, a minority behave malignantly. The aim of this study was to analyze the correlation between CD44 and MMP-2 expression with histopathological parameters in SFT. MATERIAL AND METHOD: Haemotaxylin-Eosin stained sections of 10 patients with SFT were reexamined for evaluation of histopathological parameters. Immunostaining of CD44 and MMP-2 was performed by using the streptavidin-biotin method with mouse monoclonal antibody. RESULTS: Our cases consisted of three male and seven female patients with a mean age of 54.5 years. Three patients had a history of asbest exposure. Complete resection was performed in 2 malignant (multiple masses) and 8 benign SFT cases. One intrapulmonary tumor was treated with pneumonectomy. 3 cases originated from the right and 7 from the left hemithorax. Tumor size ranged from 5 to 27cm. All cases expressed strong CD44. Only 2 malignant SFT and intrapulmonary SFT expressed focal MMP-2. CONCLUSION: Although MMP-2 positivity was observed in 2 malignant cases, CD44 positivity was not associated with malignancy criteria in solitary fibrous tumors.

The diagnostic role of capnography in pulmonary embolism.

The aim of this study was to evaluate the diagnostic contribution of alveolar dead space fraction (AVDSf) measured using capnography in patients admitted with suspected pulmonary embolism (PE). A total of 58 patients who were admitted to our hospital with suspected PE between October 2006 and January 2008 were included in this study. All patients were assessed using the Wells clinical score, capnography, computed tomographic pulmonary angiography, D-dimer measurement, lower-extremity venous Doppler ultrasonography, and V/Q scintigraphy. Forty patients (69%) had PE based on computed tomographic pulmonary angiography findings. The AVDSf value with the highest sensitivity and specificity, which was at the same time statistically significant, was 0.09. This value was consistent with the AVDSf value obtained using receiver operating characteristic analysis. In our study, the sensitivity of capnography was 70%, with a specificity of 61.1%, positive predictive value of 80%, and negative predictive value of 47.8%. The use of AVDSf in combination with any of the several scoring systems that evaluate clinical likelihood of PE and D-dimer levels resulted in higher sensitivity and specificity rates for the diagnosis of PE.

Comparison of tuberculin skin testing and T-SPOT.TB for diagnosis of latent and active tuberculosis.

The T-SPOT.TB test does not cross-react with Bacille Calmette-Guérin or most non-tuberculosis mycobacterium species, and is based on IFN-gamma responses to Mycobacterium tuberculosis-specific antigens. The objective of this study was to compare tuberculin skin test (TST) with T-SPOT.TB results used in the diagnosis of active tuberculosis (TB) as well as latent tuberculosis infection (LTBI). A total of 136 subjects participated in three different groups (47 patients with active pulmonary TB, 47 healthy persons without M. tuberculosis exposure, and 42 hospital members with a history of close contact with active TB patients). The T-SPOT.TB sensitivity (83.0%) and the negative predictive value (NPV) (82.6%) in the diagnosis of active TB were significantly higher than those of TST. The sensitivity and NPV of the TST were 38.3 and 60.8%, respectively. The T-SPOT.TB specificity (80.9%) and positive predictive value (81.3%) were lower than those of TST (95.7 and 90.0%, respectively). The performance of T-SPOT.TB and TST for diagnosing LTBI was the same (54.8%). T-SPOT.TB was superior in terms of sensitivity (83.0%); TST detected only 18, whereas T-SPOT.TB test detected 39 out of 47 patients with active TB. T-SPOT.TB is thought to have better performance than TST due to false-negative results in diagnosing active TB. However, it is considered that large prospective longitudinal studies are needed for diagnosing LTBI.

[The comparison of nicotine replacement therapy and behavioral education in smoking cessation: a study of naturalistic follow-up]. / Sigarayi birakmada nikotin replasman tedavisi ve davranis egitimi yöntemlerinin karsilastirilmasi: dogal izlem çalismasi.

In this study, we aimed to compare quitting smoking rates after behavioral education (BE) and/or nicotine replacement therapy (NRT). 610 patients applied between October 1999-April 2002 have been acknowledged and evaluated by a questionnaire including demographic variables, smoking history, smoking habits and attitudes, motivation; biochemical assay and spirometric measures were examined. One-year follow-up results and demographic variables of patients who recruited to treatment (n= 435) were analyzed by chi-square, Student-t test, one-way ANOVA and post-hoc tests. 375 (66.8 %) case were given NRT and BE; only BE (Fagerstrom < 6, not want to use of NRT, medical and economic reasons) was recommended to 186 (33.2 %) case. There was not difference between NRT and BE groups with regards to age, sex, packet year, smoking beginning age except Fagerstrom score. Smoking cessation rates for 1-year were 31.5 % in NRT group, 24.2 % in BE group, and 29.1 % in whole group (x(2)= 3.19, p> 0.05). Quitting rates were similar between age, sex, education, occupation, and complaint groups. Two groups were not statistically different with regards of smoking history and nicotine dependence. The most frequent side effect was skin reactions (7 %). The economical and medical burden of smoking increase as time goes on. According to our results, NRT and behavioral education are both efficient in smoking cessation.

[The correlation between the distant metastases and organ-specific symptoms in the patients with lung cancer]. / Akciger kanserli hastalarda uzak metastaz ile organa özgül semptomlarin iliskisi.

In this study, the correlation between distant metastases and metastatic organ-specific abnormalities in patients with lung cancer was evaluated. There were 197 patients who have lung cancer with distant metastases in this study. 141 (71.5%) of them were nonsmall cell lung cancer and 56 (28.5%) of them were small cell lung cancer. While one site of liver, brain and bone metastases were detected in 128 (64.9%) patients, remainders (69 patients, 35.1%) had surrenal, renal, pancreatic, skin, lung, thyroid, abdominal lymph node metastases. Organ-specific symptoms, findings on physical examination and abnormalities in laboratory data were detected in 121 (56.5%), 45 (21%) and 52 (24.2 %) patients, respectively. Sensitivity of predilection of organ-specific symptoms for bone, liver and brain metastases were 67%, 43% and 74% and specificity were 86%, 90% and 76%, respectively. We concluded that organ-specific abnormalities were not so effective to predict metastases in lung cancer. We considered that this result could be due to retrospective analysis and not included enough patients.