BackgroundCytochrome P450 CYP1A1 helps detoxify the potential carcinogens in tobacco smoke, it was reported that polymorphisms in the coding gene result in variation in the expression and activity levels which alter metabolism and clearance of carcinogens and therefore modify cancer risk. In this work, we aimed to identify CYP1A1 gene polymorphisms associated with lung cancer in Egyptian population and to examine the interaction effect with Tobacco smoking in modulating disease risk.MethodsA case–control study was conducted on 150 unrelated lung cancer patients and 150 unrelated control subjects. Genomic DNA was extracted and sequencing analysis of CYP1A1 gene was performed on ABI PRISM 3100 genetic analyzer.ResultsThree variants in CYP1A1 gene were identified in heterozygous forms in lung cancer patients I462V, T461N and I286T. A combined variant T461N/ I462V associated with lung cancer and those who carried this variant were 2-times more likely to develop lung cancer (OR = 2.03, 95% CI = 1.81-2.29, P = 0.04), specially the non-small cell type (NSCLC) (OR = 2.20, 95% CI = 1.93–2.50, P = 0.02). Wild type was more frequent among smoker controls (83.3%) compared to smoker lung cancer patients (54.8%), P = 0.03. Association studies to examine the interaction effect of identified variants with Tobacco smoking in modulating disease risk showed no significant associations. Identified polymorphisms showed no significant implication on the stage or the prognosis of the disease.ConclusionOur findings support that CYP1A1 polymorphisms play a role in the pathogenesis of lung cancer. In Egyptian population, CYP1A1 I462V, T461N and I286T variants were identified among lung cancer patients and combined T461N/ I462V was a risk variant for NSCLC in non smokers.

IntroductionChronic obstructive pulmonary disease (COPD) is a leading cause of disability and death. The most common cause of COPD is smoking. There is evidence suggesting that genetic factors influence COPD susceptibility and variants in several candidate genes have been significantly associated with COPD. In this study, we aimed to investigate the possible association of the TNF-α –308, SPB+1580, IL-13 –1055 gene polymorphisms and latent adenovirus C infection with COPD in an Egyptian population.Material and methodsOur study included 115 subjects (75 smokers with COPD, 25 resistant smokers and 15 non-smokers) who were subjected to spirometric measurements, identification of adenovirus C and genotyping of TNF-α –308G/A, SP-B+1580 C/T and IL-13 –1055 C/T polymorphisms by real-time PCR.ResultsThe adenovirus C gene was identified in all subjects. The distribution of TNF-α genotypes showed no significant differences between different groups. However, homozygous A genotype was associated with a significant decrease in FEV1, FEV1/FVC and FEF25/75% of predicted in COPD (p < 0.05). As regards SP-B genotypes, resistant smokers had a significantly higher homozygous T genotype frequency compared to COPD and non smokers (p = 0.005). Interleukin 13 genotypes showed no significant difference between different groups. There was a significant decrease in FEF25/75% of predicted in T allele carriers in COPD patients (p = 0.001).ConclusionsThe COPD is a disease caused by the interaction of combined genes and environmental influences, in the presence of smoking and latent adenovirus C infection, TNF-α –308A, SPB +1580 T and IL-13 –1055 T polymorphisms predispose to the development of COPD.

BackgroundSeveral studies have reported the role of CYP2A6 genetic polymorphisms in smoking and lung cancer risk with some contradictory results in different populations. The purpose of the current study is to assess the contribution of the CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 gene polymorphisms and tobacco smoking in the risk of lung cancer in an Egyptian population.MethodsA case-control study was conducted on 150 lung cancer cases and 150 controls. All subjects were subjected to blood sampling for Extraction of genomic DNA and Genotyping of the CYP2A6 gene SNPs (CYP2A6*2 (1799 T > A) rs1801272 and CYP2A6*9 (− 48 T > G) rs28399433 by Real time PCR.ResultsAC and CC genotypes were detected in CYP2A6*9; and AT genotype in CYP2A6*2. The frequency of CYP2A6*2 and CYP2A6*9 were 0.7% and 3.7% respectively in the studied Egyptian population. All cancer cases with slow metabolizer variants were NSCLC. Non-smokers represented 71.4% of the CYP2A6 variants. There was no statistical significant association between risk of lung cancer, smoking habits, heaviness of smoking and the different polymorphisms of CYP2A6 genotypes.ConclusionThe frequency of slow metabolizers CYP2A6*2 and CYP2A6*9 are poor in the studied Egyptian population. Our findings did not suggest any association between CYP2A6 genotypes and risk of lung cancer.

Aim of the studyComplement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti-tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism in CFH gene with lung cancer and the interaction with cigarette smoking.Material and methodsThis case-control study included 80 primary lung cancer patients and 106 control subjects who were genotyped for Try402His (rs1061170) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsVariant genotypes (Tyr/His and His/His) were overpresented among patients compared to controls (p = 0.03, OR = 2.510, 95% CI: 1.068–5.899), and the frequency of variant H allele was significantly overexpressed in cases compared to controls (p = 0.021). Tyr/His genotype was identified in 100% of small cell lung cancer (SCLC) patients vs. 34.5% of non-SCLC (NSCLC), while 20.7% of NSCLC patients were homozygous for the variant allele (His/His) (p = 0.001). Binary logistic regression analysis revealed a 2.5 times greater estimated risk for NSCLC than for SCLC among variant allele carriers, and a 7.3-fold increased risk of lung cancer among variant allele smoking carriers vs. 1.3-fold increased risk among wild allele smoking carriers. Moreover, the stage of cancer positively correlated with smoking and pack-years in allele H carriers, and the correlation was stronger among those who were homozygous for it (His/His) than those who were heterozygous (Tyr/His).ConclusionsCFH 402H variant is a smoking-related risk factor for lung cancer, particularly the NSCLC.

IntroductionTGF-β1 is a cytokine with many different effects on cell proliferation, differentiation and inflammation and can protect against the development of COPD. This work aims to study the association between COPD and the TGF-β1 gene genotypes.Material and methodsThe study included 70 males: 25 smokers with COPD, 25 resistant smokers, and 20 normal non-smokers as the control. They were subjected to spirometry pre- and post-bronchodilator (FEV1, FEV1/FVC), estimation of serum level of TGF-β1 gene by PCR and RFLP.ResultsThe percent of Pro-Leu was 28% in the COPD group, 84% in the resistant smokers group and 85% in the control group. There was a highly significant statistical difference in FEV1% of predicted associated with the distribution of TGF-β1 gene genotypes: 56.9 ±8.4% with Pro-Leu genotype and 35.5 ±8.8% with Leu-Leu genotype in COPD patients, 93.2 ±6.2% with Pro-Leu genotype and 86.7 ±0.9% with Leu-Leu genotype in the resistant smokers group.ConclusionsThe Pro-allele genotype is associated with increased production of TGF-β1, which has a protective role against the development of COPD and is important in preserving the decline of FEV1 in COPD patients.

Objectives: To study lung diseases in chronic HCV infection and vice versa and to find immunological and/or hereditary interrelating factors. Material and Methods:Study included 134 individuals, all were subjected to screening for anti-HCV antibodies by ELISA, HCV-RNA by real time PCR, pulmonary function tests, quantitative assay of interferon gamma and alpha-1-antitrypsin in serum by ELISA and genotyping of alpha-1-antitrypsin gene by Light Cycler PCR.Results: 76.5% of chronic HCV patients had abnormal PFT (P = 0.03), mainly reduced DLCO and reversible airway obstruction, and 41.6% of chest diseased patients were HCV-positive with a significant decrease in large and small airways functions. Interferon therapy improved PFT parameters. Only 33% of chronic HCV infection affected by chest abnormality responded to interferon therapy while 50% of chest free patients did. Serum IFN-γ was higher in HCV and chest patients than in control (P=0.02). All serum α1AT deficient patients had M/null genotype. Conclusions:A pathogenic role of chronic HCV infection in lung diseases is evident. Interferon treatment may reduce chest complications and improve pulmonary functions. However, chest affection may reduce the response to interferon treatment. M/null genotype of α1AT gene might play a role in chronic HCV infection and chest co-affection.

Background: Gene-gene and gene-environment interactions play an important role in cancer susceptibility. In this work, we studied the association of XRCC1 rs25487, ERCC1 rs735482, and CHRNA3 rs1051730 variants with lung cancer and assessed the modulatory effect of potential interaction between these variants on disease risk. Results: In this study, 86 primary lung cancer patients and 64 control subjects were genotyped for CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 by real-time PCR. The frequency of the three studied variants was higher among lung cancer patients than in control subjects, but with no statistical significance. ERCC1 rs735482 variant was associated with 6.9-fold increased risk to develop lung cancer among smokers (p = 0.03). Concomitant presence of CHRNA3 and ERCC1 wild alleles was associated with 2.7-fold elevated risk of lung cancer (p < 0.0001), while concomitant presence of CHRNA3 rs1051730 variant allele with ERCC1 wild allele was associated with 20-fold elevated risk (p < 0.000). Concomitant presence of both variants, ERCC1 rs735482 and CHRNA3 rs1051730, was associated with 9.9-fold elevated risk (p < 0.0001). Meanwhile, the concomitant presence of XRCC1 rs25487 with either ERCC1 rs735482 or CHRNA3 rs1051730 or both was not associated with increased risk of the disease. Conclusion: Our results emphasize the role of gene-gene interaction in the pathogenesis of lung cancer. Largescale further studies to clarify the underlying mechanisms are needed.

Background The prognostic value of Platelet-to-lymphocyte ratio (PLR) in patients with malignant pleural mesothelioma is still indistinct. We conducted this study to assess the prognostic significance of pretreatment PLR in patients with MPM. Aim of the Work to assess the prognostic significance of pre-treatment PLR in patients with MPM. Material and Methods we retrospectively reviewed 1!0 patients treated for MPM with chemotherapy in Ain-Shams University hospital, Clinical Oncology department between January 2013 and December 2017. Pre-treatment CBC was available for the 110 patients to calculate PLR by dividing the absolute platelet count by the absolute lymphocytic count. Results Out of 110 patients with available pre-treatment complete blood picture, population age ranged from 28 to 70 years. Male to female ratio was 5:6 .Epithelioid subtype represent 85% of cases. Stages III and IV present 48.2% and 35.5, respectively while stages I and II present 3.6% and 12.7%, respectively. The median PLR in the study population was found to be 177.9, Conclusion PLR is an easy , reproducible and inexpensive prognostic factor that needs to be more investigated in MPM.