Risk Of NSCLC Research Articles

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 THE UROKINASE PLASMINOGEN ACTIVATION SYSTEM POLYMORPHISMS AND NSCLC IN CHINESE POPULATION

Aim: To evaluate the influence of uPA and uPAR gene polymorphisms in the susceptibility to NSCLC.Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited and matched according to age and gender. The SNPs distributed in uPA and uPAR gene were selected for genotyping. The association between genotype and NSCLC risk was evaluated by computing the OR and 95% CI with multivariate unconditional logistic regression analyses.Results: Patients with the uPAR rs344781 T allele had a reduced risk of developing SCC patients (OR = 0.742; 95% CI = 0.579 - 0.950; P = 0.0176), especially a risk of developing male SCC patients (OR = 0.722; 95% CI = 0.546 - 0.954; P = 0.0219). And the uPAR rs344781 C/C allele homozygote was associated with an increased risk of SCC in patients (OR = 1.713; 95% CI = 1.145 - 2.563; P = 0.0083). However, neither allele frequencies nor genotype frequencies in uPA rs4065 were associated with NSCLC (P > 0.05).Conclusions: Our results revealed that genetic polymorphisms of uPAR rs344781 were associated with the risk of developing SCC (squamous cell carcinoma) in a Chinese population.

Association between polymorphisms in the XRCC1 gene and the risk of non-small cell lung cancer.

Here, we have reported a case-control study investigating the association between XRCC1 codons Arg194Trp, Arg280His, and Arg399Gln and the development of NSCLC. NSCLC patients (N = 245) and healthy controls (N = 257) were randomly selected from the Huaihe Hospital between March 2012 and August 2014. DNA extracted from the patient and control blood samples were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to assess the genotyping of XRCC1 Arg194Trp, Arg280His, and Arg399Gln. Multivariate logistic regression analyses revealed an association between the expression of the AA genotype and A allele genotypes and a significantly increased risk of NSCLC, compared to the GG genotype [95% confidence interval (CI); Odd's ratio (OR) = 2.82 (1.141-5.86) and 1.67 (1.17-2.37), respectively]. The potential association between the A allele of XRCC1 Arg399Gln and the risk of NSCLC was more evident in smokers (95%CI; OR = 1.70; 1.11- 2.63). In conclusion, the XRCC1 Arg399Gln polymorphism was found to be associated with increased risk of NSCLC, especially in tobacco smokers.

Genome Wide Association Study (Gwas) for Identification of Single Nucleotide Polymorphisms (Snps) Associated with Individuals Presenting Extreme Phenotypes of Tobacco Induced Non-Small Cell Lung Cancer (Nsclc) Risk

ABSTRACT Aim: We analyzed the genome of individuals presenting extreme phenotypes of sensitivity and resistance to develop tobacco induced NSCLC to identify SNPs associated with these phenotypes. For this purpose, we used one of the most powerful GWAS platforms available. We hypothesized that SNPs may modulate individual susceptibility to carcinogens and that selection of extreme phenotypes would enrich the frequencies of alleles that contribute to the trait, thus increasing the power to identify them. Methods: From an identification cohort (n=3631) we selected caucasian heavy smokers that either developed NSCLC at an early age (cancer-cohort) or that did not present NSCLC at an advanced age (cancer-free cohort). We analyzed their genomic DNA using the array Illumina HumanOmni 2.5 Quad that includes over 2 million powerful markers selected from the 1000 Genomes Project, targeting genetic variation down to 1% minor allele frequency. Statistical significance of SNPs was calculated using logistic regression and Fisher's test. Results: 96 patients (48 per cohort) were selected. Mean age for the cancer and cancer-free cohorts was 49 years (range 38-55) and 76 years (72-84). Mean tobacco consumption was 41 pack-years (range 18-99) and 68 pack-years (40-120). GWAS identified 8 SNPs differentially expressed by logistic regression and 54 SNP by Fisher's test (p Function Gene Oncogenes MSX2 SOX11 Tumor supressors CSMD1 FOXF1 Tobacco induced NSCLC ABCB5 Regulators of transcription DROSHA HDAC9 KIAA0947 Regulators of inflammation PellinoE3 TRIM9 Related with cancer ABHD6 GRIK1 RAB40B SCN1A SLC24A2 SLC25A26 ZFYVE26 Conclusions: We identified candidate SNPs associated with the risk of developing tobacco-induced NSCLC in individuals with extreme phenotypes. Several identified SNPs were located within or near genes that constitute potentially relevant targets for modulation of cancer risk. Validation of the most significant SNPs in an independent set of individuals with similar phenotypes, selected from the EPIC-Spain project (www.epic-spain.com, n=40,000) is ongoing. Disclosure: All authors have declared no conflicts of interest.

Transforming growth factor-β1 rs1800470 polymorphism is associated with lung cancer risk: a meta-analysis.

BackgroundTransforming growth factor-β1 is a member of a large class of polypeptides that regulate the proliferation, differentiation, and carcinogenesis of epithelial cells. The rs1800470 polymorphism influences transforming growth factor-β1 expression and has been associated with lung cancer susceptibility. However, the association between the rs1800470 polymorphism and lung cancer risk remains controversial. Thus, a meta-analysis was conducted.Material/MethodsWe comprehensively searched PubMed and EMBASE databases. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models or fixed-effects models.ResultsOverall, there was a significant association between rs1800470 polymorphism and lung cancer susceptibility (OR=1.23; 95%CI, 1.03–1.47; P=0.02). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with lung cancer in Asians (OR=1.26; 95%CI, 1.01–1.57; P=0.04). However, we did not find any significant association between this polymorphism and lung cancer risk in Caucasians (OR=1.04; 95%CI, 0.60–1.82; P=0.88). In the NSCLC subgroup, we found that rs1800470 polymorphism could increase NSCLC risk (OR=1.36; 95%CI, 1.06–1.74; P=0.02).ConclusionsThis meta-analysis suggested that rs1800470 polymorphism was a risk factor of lung cancer.

Common Genetic Variants in 53BP1 Associated with Nonsmall-cell Lung Cancer Risk in Han Chinese

The study investigated several common SNPs in the tumor protein p53 binding protein 1 gene and tumor protein p53 gene in 640 lung cancer cases and 685 controls in Han Chinese to determine if these single nucleotide polymorphisms (SNPs) were associated with lung cancer risk. Several studies indicated that SNPs in the 53BP1 and TP53 gene are associated with cancer risk. We investigated the association between common SNP variants in the 53BP1, TP53 gene and lung cancer risk. We used real-time PCR method to investigate the genotypic frequencies of rs2602141, rs560191 and rs689647 in 53BP1 and rs1042522 in TP53 in 640 cases of lung cancer and 685 controls. SNPs rs2602141, rs560191 and rs689647 in 53BP1 were in complete linkage disequilibrium in Han Chinese. The frequencies of the G/G, G/T and T/T genotypes of rs2602141 were 17.5, 50.3 and 32.2% in cases and 21.0, 49.3 and 29.6% in controls, respectively and distributions were not significantly different (p = 0.236). The rs2602141 T/T genotype increased NSCLC risk (OR = 1.56, 95% CI = 1.10-2.21). The genotype distribution frequency of rs1042522 does not demonstrate significant differences between cases and control group. 53BP1 and TP53 gene interactions were not associated with lung cancer risk.

Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: A case control study

Interleukin 8 (IL-8), is a proinflammatory chemokine, has been reported to have angiogenic activity and to be responsible for tumor-associated angiogenesis in several cancers. In this study, we aimed to study the (IL-8) gene polymorphism in relation with risk development of non small cell lung cancer in Tunisian patient. Two single nucleotide polymorphisms (-251T/A [rs4073], +781C/T [rs2227306]) of the IL-8 gene were screened in 170 patients with NSCLC and 225 healthy controls by PCR-RFLP. Significant association for the IL-8 -251T/T genotypes (P=0.004) and an increased significant frequency of IL-8 -251T allele were noted in the patient's group (P=0.0007). Clinical analysis indicated a borderline positive association of IL-8 -251T allele among adenocarcinoma patients (P=0.003). Our study indicated that IL-8 -251T allele was highly associated with large tumor size and high grade stage of NSCLC. Moreover, a significantly increased risk of NSCLC was associated with IL-8 +781C allele in patients with large tumor size (T3 and T4) (P=0.004). IL-8 mRNA expression was found highly expressed in NSCLC patients compared to healthy controls. The same higher level was even found in patients carrying IL-8 -251T/T genotype. Our results indicated that the IL-8 promoter polymorphism is associated with NSCLC risk.

Abstract 4079: Proanthocyanidins reactivate silenced tumor suppressor genes p16INK4 a and Cip1/p21 by reducing DNA methylation and increasing histone acetylation in human non-small cell lung cancer cells

Abstract Non-small cell lung cancer (NSCLC) represents α80% of all types of lung cancer and includes squamous cell carcinoma, adenocarcinoma and large-cell carcinomas. The risk of NSCLC is greatly affected by epigenetic modulations in lung cells. Cancer epigenetics deal with important processes including DNA methylation and histone modification patterns that can either activate oncogenes or inactivate tumor suppressor genes, the crucial steps in tumor development. The study of epigenetic regulations has become a new target for early detection, risk assessment, prognosis and cancer therapy. Therefore, to develop more effective therapeutic agents for lung cancer, we sought to determine the effect of grape seed proanthocyanidins (GSPs), which have been shown to have anti-carcinogenic effects in some tumor models, on epigenetic modulation in NSCLC cells. For this purpose two genetically different NSCLC cell lines, A549 (p53 wild type) and H1299 (p53 mutant), were selected and treated with lower concentrations of GSPs (5, 10, 20µg/ml) for six days. The status of DNA global methylation patterns was determined by immunostaining using a monoclonal antibody specific to 5-methylcytosine (5-mC) and global DNA methylation assay. Treatment of cells with GSPs resulted in a dose-dependent decrease in 5-mC-positive cells as compared to non-GSPs-treated controls. These data were verified by dot-blot analysis. Global methylation levels of DNA as obtained from quantitative DNA methylation assay reduced to 36±5% in A549 cells and 31±5% in H1299 cells with the treatment of GSPs. The expression levels of the DNA methyltransferases, e.g., DNMT1, DNMT3a and DNMT3b, were higher in non-GSPs treated cells and reduced with GSPs treatment as analyzed by western blotting and real-time PCR. The hypermethylation of DNA in NSCLC cells may lead to silencing of tumor suppressor genes, thereby contributing to the risk of lung cancer. Therefore, we analyzed the methylation status of the various tumor suppressor genes, like p16INK4a, Cip1/p21 and RASSF1A through methylation specific PCR and the relative repression levels of their mRNA were analyzed using real-time PCR, which indicated that the DNA methylation levels of these tumor suppressor genes were reduced in GSPs treated cells, and that resulted in re-expression of the mRNA and proteins of silenced tumor suppressor genes compared to non-GSPs treated cells. GSPs decreased histone deacetylase activity and increased the levels of histone acetylation which included the acetylated lysine 9 and 14 on histone H3 (H3-Lys 9 and 14) and acetylated lysine 5 and 12 on histone H4 but decreased the levels of methylated H3-Lys 9. Together, our study provides new insight into the epigenetic mechanism of action of GSPs that may have important implications for epigenetic therapy of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4079. doi:1538-7445.AM2012-4079

Clinical and Prognostic Significance of Promoter Polymorphism (-31GC)of Anti Apoptotic Gene Survivin (BIRC5) in North India Patients with Non Small Cell Lung Cancer

Background: Apoptotic inhibitor gene survivin regulates apoptosis and cell cycle progression. Functional polymorphism in the promoter region of survivin influences its expression may lead to the development of several cancers including lung cancer. Our study aimed to investigate the association of survivin-31G>C polymorphism with the risk of NSCLC in Indian population. Methods: A hospit al-based case control study of 136 cases and 136 age-gender matched healthy controls was performed by PCR-RFLP. Results: Our findings reveal that a statistically increased risk and poor survival was associated with the BIRC5 -31CC genotype (OR 3.13, 95% CI 1.57- 6.25) compared to the genotype containing G allele GC (OR 1.22, 95% CI 0.69-2.14). In addition significant association was found with stage and distant metastasis status of NSCLC patients. Conclusions: Our results conclude that the function polymorphism (-31G>C) in the promoter of survivin gene is associated with risk and susceptibility to NSCLC.

Impact of MDM2 SNP309T>G Polymorphism: Increased Risk of Developing Non Small Cell Lung Cancer and Poor Prognosis in Indian Patients

Background: MDM2 is an important negative regulator of the TP53 pathway, over expressed in many cancers as oncoprotein. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus play an important role in carcinogenesis. Aim and methods: To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of non small cell lung cancer, we conducted a hospital-based, case–control study of 136 Indian patients diagnosed with NSCLC and 136 cancer-free controls and investigated the association between genetic variation in the promoter region of MDM2 (c.–51309G4T, rs2279744:g.G4T) and the risk of developing NSCLC by tetra-primer ARMS-PCR and ASO-PCR. Results: Compared with the MDM2-2580TT genotype, we found that the MDM2-309G variant genotypes were associated with an increased risk of NSCLC in Indian patients [OR 3.88 (1.82-8.27) RR 1.94 (1.27-2.96) RD 32.6 (15.7-49.6) p 0.0004 for GG and OR 2.60 (1.49-4.57) RR 1.52 (1.20-1.93) RD 23.16 (10.3-36.0) p 0.0009 for GT genotype]. GG genotype was found to be associated with poor survival outcome of NSCLC patients and in addition significant association was observed with stage (p 0.01) and metastasis status (p 0.002) of NSCLC patients. Conclusion: Genetic polymorphism in cell cycle regulatory genes MDM2 contribute to the risk of developing NSCLC in Indian Patients. In addition G allele was associated with an increased risk and poor survival outcome than T allele.

Biological and Clinical Implications of Functional Promoter Polymorphism of CASPASE 9 Gene in Non Small Cell Lung Cancer Patients

Purpose: The study was conducted to determine the impact of promoter polymorphism in CASP9 gene on susceptibility and prognosis of Non Small Cell Lung Cancer patients of Indian origin. Patients and methods: Present case control study includes newly diagnosed 160 NSCLC patients and 160 healthy controls. Promoter polymorphism (-712C>T, rs4645981) in CASP9 gene was investigated using PCR-RFLP technique. Results: Our findings reveal that a statistically significant increased risk of about 2.6 fold was associated with homozygous TT genotype of CASP9 (-712C>T) promoter polymorphism (OR 4.3, 95%CI 2.2-8.3, p=0.0000) in Indian population .In addition smokers were at high risk for NSCLC which was more predominant in heavy smokers with pack-year >40 and in cigarette or beedi smokers. Compared to males, females were at high risk; about 2.3 fold more in association with homozygous TT genotype [OR, 3.9(1.9-8.2) in males vs. 6.2(1.4-27.1) in females]. Significant association was observed between advanced TNM stage (p<0.0001) and distant metastasis status (p<0.0001) of NSCLC patients with the polymorphism. Patients homozygous for T allele exhibited a significant poor overall survival compared with patients displaying CT+TT or CT or CC genotype (Median survival 6.0 vs. 9.0, 11.0, and 30.0, months respectively, p<0.0001). Also advanced stage patients with TT genotype showed lower median survival time than early stage NSCLC patients (Median 5.0 vs. 9.0 months respectively). Conclusion: The functional polymorphism (-712C>T) in the promoter region of CASP9 gene is associated with risk and susceptibility to NSCLC in north Indian population, and also is an important factor for poor prognosis in patients with NSCLC.

Investigation of lifestyle risks exposure as response predictor of gefitinib in non-small cell lung cancer patients.

e18070 Background: As smoking was significant negative predictor to EGFR-TKI treatment and act as risk for NSCLC too, our curiosity was evoked to do the pilot investigation on the relationship betw...

Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China

BackgroundCigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are also considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear.MethodsWe collected the data of 150 cases and 150 age-matched and sex-matched controls on a Hospital-Based Case-Control Study in China. Face to face interviews were conducted using a standardized questionnaire. Gene polymorphism and methylation status were measured by RFLP-PCR and MSP, respectively. Logistic regressive model was used to estimate the odds ratios (OR) for different levels of exposure.ResultsAfter adjusted age and other potential confounding factors, smoking was still main risk factor and significantly increased 3.70-fold greater risk of NSCLC as compared with nonsmokers, and the ORs across increasing levels of pack years were 1, 3.54, 3.65 and 7.76, which the general dose-response trend was confirmed. Our striking findings were that the risk increased 5.16, 8.28 and 4.10-fold, respectively, for NSCLC with promoter hypermethylation of the p16, DAPK or RARβ gene in smokers with CYP1A1 variants, and the higher risk significantly increased in smokers with null GSTM1 and the OR was 17.84 for NSCLC with p16 promoter hypermethylation, 17.41 for DAPK, and 8.18 for RARβ in smokers with null GSTM1 compared with controls (all p < 0.01).ConclusionOur study suggests the strong combined effects of cigarette smoke, CYP1A1 and GSTM1 Polymorphisms, hypermethylations of p16, DAPK and RARβ promoters in NSCLC, implying complex pathogenesis of NSCLC should be given top priority in future research.

Association between XRCC1 gene haplotype tagging single nucleotide polymorphisms and non-small cell lung cancer in Korean patients.

1541 Background: Single nucleotide polymorphisms (SNPs) in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. This study aimed to investigate the relationship between SNPs and haplotypes of the XRCC1 gene on the risk of NSCLC in Korean patients. Methods: Genotyping for SNPs in XRCC1 was performed using Sequenom's (San Diego, CA, USA) high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 140 NSCLC patients and 217 controls. Haplotype frequency estimation and association analysis were performed via permutation testing using the Haploview version 4.0 software (Broad Institute of MIT and Harvard, Cambridge, MA, USA). Results: Only an individual SNP of XRCC1, rs1001581, was associated with increased risk of NSCLC in Korean patients (adjusted odds ratio (OR), 2.121; 95% confidence interval (CI), 1.06-2.32; Ptrend = 0.004). Seven possible haplotypes were demonstrated in this study (if haplotype frequency was > 1%). Of seven haplotypes, the frequency of wild haplotype was 0.109 and wild haplotype showed protective effect of NSCLC risk in Korean patients (OR, 0.433; 95% CI, 0.299-0.489; p = 0.002). The association between wild haplotype and decreased risk of NSCLC and the relationship between rs1001581 and increased risk of NSCLC were stable on permutation testing, respectively (p = 0.02 and p = 0.04). Presence of rs1001581 and increased risk of NSCLC was stable on permutation testing among never- and ever-smokers (p = 0.007 and p = 0.039, respectively). The association between wild haplotype and decreased risk of NSCLC was stable on permutation testing only ever-smokers (p = 0.021). Conclusions: These findings suggest that wild haplotype consisted of wild 9 SNPs showed protective role against development of NSCLC in ever-smokers and rs1001581 non-coding SNP showed increased risk of NSCLC among never- and ever-smokers in Korean patients. Thus, this study presents several novel aspects on genetic susceptibility to NSCLC and larger studies of the role of rs1001581 for NSCLC risk would be needed regardless of smoking history. No significant financial relationships to disclose.

Genotype analysis of the VNTR polymorphism in the SMYD3 histone methyltransferase gene: Lack of correlation with the level of histone H3 methylation in NSCLC tissues or with the risk of NSCLC

Fabrice Barl esi, Giuseppe Giaccone*, Marielle I. Gallegos-Ruiz, Simone W. Span, Pierre Lefesvre, Frank A.E. Kruyt and Jose Antonio Rodriguez Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands Universit e de la M editerran ee, Assistance Publique Hopitaux de Marseille, Thoracic Oncology, Marseille, France Medical Oncology Branch, CCR, National Cancer Institute, NIH, Bethesda, MD Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Spain

PD2-3-8: -2518 MCP-1 and Interleukin-4 VNTR polymorphisms and NSCLC risk

PD2-3-8: -2518 MCP-1 and Interleukin-4 VNTR polymorphisms and NSCLC risk

Rare SP‐A alleles and the SP‐A1‐6A4 allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.

O-261 Polymorphic phase I & phase II enzymes confer a higher risk of NSCLC in Australians

O-261 Polymorphic phase I & phase II enzymes confer a higher risk of NSCLC in Australians

Chest wall invasive non-small cell lung cancer: Patterns of failure and implications for a revised staging system

To assess outcomes and patterns of failure for chest wall invasive non-small cell lung cancer (T3 or IIIA NSCLC), data were acquired prospectively on 47 consecutive patients at a single institution over 6 years. Preresectional stagings included bone scan, head and chest/abdominal computed tomography, and mediastinoscopy. There were 25 superior sulcus tumors (radiation and/or chemotherapy followed by resection) and 22 other chest wall invasive NSCLCs (resection alone). There were no perioperative deaths. Seventeen patients (36%) had an operative complication (median length of stay increased from 7 to 12 days; p < 0.05). A complete pathologic resection was achieved for 44 of 47 patients (94%). The median survival was 38 months (actuarial 2- and 5-year survival rates of 62% and 50%, respectively). Median lengths of survival for superior sulcus and other chest wall tumors were 36 and > 60 months, respectively. Significant univariate predictors of decreased overall and cancer-free survival were poor performance status, positive margins, and positive lymph nodes. Recurrence was observed in 22 of 47 patients (46%) at a median of 8 months (range 2-24); patterns of failure were in the ipsilateral chest (n = 2; 4%) and at a distant site (n = 15; 32%) or both (n = 5; 11%). The operative risk for chest wall invasive NSCLC is acceptable, even after neoadjuvant therapy, allowing for a 94% complete resection rate. The survival of this subset of stage IIIA patients may warrant a reappraisal of the international staging system.