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Summary: Background: Human lung cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. However, the biallelic EcoRI polymorphism of this gene has not been studied in lung cancer. With this allelic association study, we aimed to investigate the impact of polymorphisms of the NME1 gene on the susceptibility to and severity of non-small cell lung cancer (NSCLC). Methods: Through a case-control study design, genomic DNA samples of 255 NSCLC patients and 303 controls, who were age and sex-matched and recruited from the health check-up unit, were subjected to polymorphism analysis with polymerase chain reaction-restriction fragment length polymorphism technique. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of the metastasis-suppressor gene NME1 in the susceptibility to and severity of NSCLC. Results: Overall, the genotype frequencies of NME1 gene were significantly different between lung cancer patients and controls (p <0.0001), and also different between patients with lung cancers of various stages (p <0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen in patients homozygous (+/+) for variant allele (an OR of 4.02, 95% CI 2.39–6.76; p <0.0001). Patients carrying a variant polymorphic homozygote (+/+) also had a tendency to advanced disease (p =0.001). Conclusion: A significant association between the polymorphisms of NME1 gene and the susceptibility to and severity of lung cancer was demonstrated. [Copyright &y& Elsevier]

Summary: Background: Genetic polymorphisms in the promoter region of the tumor necrosis factor-α (TNF-α) gene are involved in the regulation of expression levels and have been associated with various inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter region of the TNF-α gene (-308 G/A and -238 G/A) for their role in the susceptibility to and severity of non-small cell lung cancer (NSCLC), by means of an allelic association study. Methods: Using a case–control study design, lung cancer patients (n =202) and appropriate age- and sex-matched controls recruited from the health check-up unit (n =205) were subjected to genotype analysis for these polymorphisms, using a high-throughput allelic discrimination method. Results: Genotype was analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique with genomic DNA isolated from peripheral blood lymphocytes. Overall, the distribution of the genotype frequencies of TNF-α-308 A/G and -238 A/G were significantly different between the lung cancer patients and the healthy controls, and also different between patients with lung cancers of various stages (p <0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with TNF-α-308 AA/GA genotypes against GG genotype (an OR of 3.75, 95% CI 2.38–5.92, p <0.0001), and lower ORs were seen for individuals with TNF-α-238 AA/GA genotypes against GG genotype (an OR of 0.26, 95% CI 0.13–0.50, p <0.0001). The patients carrying a homologous AA or heterologous GA genotype at TNF-308 (p =0.017), or a homologous GG genotype at TNF-238 (p =0.001), had a tendency to advanced disease. Conclusions: A significant association between the 308 G/A and 238 G/A polymorphisms in the promoter region of TNF-α and the susceptibility to lung cancer was demonstrated. Also, these two polymorphisms were associated with the severity of lung cancer. The -308 A allele has a promotive effect for lung cancer development and progression, whereas the -238 A allele has a protective function against lung cancers. [Copyright &y& Elsevier]

Summary: Study objectives: Interleukin-10 (IL-10) is mainly an anti-inflammatory cytokine produced by a number of cells including normal and neoplastic cells and has been implicated in autoimmunity, transplantation tolerance and tumorigenesis. Inter-individual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether polymorphisms in the IL-10 gene promoter were involved in predisposing an individual to non-small cell lung cancer (NSCLC). Patients: A total of 154 patients with non-small cell lung cancer were recruited into this study, together with 205 age- and gender-matched healthy smokers acting as control subjects. Measurements: Polymorphisms of sites within the promoter region of IL-10 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism technique on genomic DNA isolated from peripheral lymphocytes. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of IL-10 promoter to the susceptibility to NSCLC. Results: The distribution frequencies of genotypes of IL-10-1082, -819 and -592 were significantly different between NSCLC patients and controls. Pearson χ 2 analysis showed that the frequency for IL-10-1082 G allele, IL-10-819C allele and IL-10-592C allele was independently higher in NSCLC patient group than that in the control group. Higher odds ratios (ORs) for NSCLC were seen for individuals with G allele of IL-10-1082 [OR=5.26, 95% CI 2.65–10.4, p <0.0001], C allele of IL-10-819 [OR=1.57, 95% CI 1.15–2.16, p =0.005], C allele of IL-10-592 [OR=1.59, 95% CI 1.15–2.19, p =0.005]. Conclusion: The polymorphisms of IL-10 genes were significantly associated with the occurrence of NSCLC. [Copyright &y& Elsevier]

Correlation between p53 autoantibodies (p53 Abs) titers and the efficacy of Taiwanese lung cancer patients undergoing chemotherapy has never been investigated. Our present study aimed at evaluating putative possibility of using p53 Abs levels as a model system to monitor effect of chemotherapy and prognosis prediction of lung cancer.The prevalence of p53 Abs in lung cancer patients and temporal alteration of p53 Abs titers in lung cancer patients carrying p53 Abs were investigated by using ELISA and Western blot analysis.p53 Abs was detected in 17 of 277 (6.14%) lung cancer patients, the positivity of p53 Abs in patients with small cell lung carcinoma and non-small cell lung carcinoma was 4.88% and 6.36%, respectively. No significant association between p53 Abs and patients'' clinical manifestations was found. Titer of p53 Abs was decreased in 6 of 17 p53 Abs-carrying patients after chemotherapy. However, the decreasing p53 Abs titers were not correlated with patients'' survival or chemotherapeutic efficacy.The prevalence of p53 Abs in Taiwanese lung cancer is much lower than that in Caucasians. It is unlikely that p53 Abs titer could be a monitoring indicator for the chemotherapeutic efficacy or a prognosis indicator of lung cancer. [Copyright &y& Elsevier]

Abstract: Background: Urokinase plasminogen activating (uPA) system is implicated in neoplastic progression. High tissue levels of uPA system components correlate with a poor prognosis in lung cancer. The present study examined the single nucleotide polymorphisms (SNPs) of uPA and the corresponding receptor, uPAR, for exploring their roles in non-small cell lung cancer (NSCLC). Methods: The allele frequencies and genotype distributions of uPA rs4065 C/T and uPAR rs344781 (−516 T/C) among 375 NSCLC cases and 380 healthy controls were examined using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. Putative association between the above SNPs and clinicopathological characteristics of NSCLC were also analyzed. Results: The genotype frequencies of the variant homozygotes of uPA and uPAR were significantly different between NSCLC and control subjects. Significant association was also observed between the examined genotypes and disease stage of NSCLC. Logistic regression analysis revealed that individuals with uPA rs4065 TT genotype have higher odds ratios (ORs) for lung cancer. Whereas, subjects with uPAR-344781 CC genotype have lower ORs for lung cancer. The patients carrying a homozygous TT genotype at uPA rs4065, or at least a T allele at uPAR-344781 (−516), had a tendency to develop advanced disease. Conclusions: Our results revealed that genetic polymorphisms of the uPA rs4065 C/T and uPAR rs344781 (−516 T/C) were associated with the susceptibility and severity of NSCLC. [ABSTRACT FROM AUTHOR]