Association between secondhand smoke exposure and hypertension in never smokers: a cross-sectional survey using data from Korean National Health and Nutritional Examination Survey V, 2010-2012.

OBJECTIVES: Secondhand smoke (SHS) exposure is associated with cardiovascular disease. This study aims to determine the association between SHS exposure estimated by questionnaire and hypertension in Korean never smokers. SETTING: Korean National Health and Nutrition Examination Survey (KNHANES) V was conducted from 2010 to 2012. PARTICIPANTS: We selected the never smokers aged over 20 years who answered the question about the SHS exposure. PRIMARY AND SECONDARY MEASURES: SHS exposure in both the home and work place was estimated using a self-reporting questionnaire. We investigated the association between SHS exposure and hypertension by using multivariate analysis. And we evaluated the mean systolic and diastolic blood pressure values according to SHS exposure after adjusting for possible confounding factors. All analyses were stratified by women and men. RESULTS: There were 10 532 (women 8987 and men 1545) never smokers. We divided the subjects into three groups according to the amount of SHS exposure: none-group I, <2 hour/day-group II and ≥2 hour/day-group III. Using multivariate analysis, hypertension was more commonly associated with group III than group I in women (adjusted OR 1.50, 95% CI 1.00 to 2.04, p=0.011). Adjusted mean systolic and diastolic blood pressure values in women who were not taking antihypertensive medication were significantly elevated in group III by 2.3 and 1.7 mm Hg, respectively. CONCLUSION: SHS exposure is significantly associated with hypertension in women never smokers.

Investigation of Trapezoidal Well for Improving the Light Efficiency in AlGaInP-Based Light-Emitting Diodes.

We investigated high-brightness light emitting diodes appropriate for general lighting applications in terms of their optical behaviors and device performances according to the insertion of the sloped barrier between the well and the barrier and changing the sloped barrier thickness. As the sloped barrier thickness was increased from 0 to 5 nm, radiative recombination efficiency and device performances significantly improved, due to the suppression of carrier overflow by the stronger capture of carriers and the shortening of the carrier lifetime in the active region owing to the built-in quasi-electric field. At a further increase in the sloped barrier thickness to 10 nm, however, the optical and device performances started to degrade because of the loosening of the quantum confinement effect in the active region and due to the saturation of the improvement of the carrier capture by the sloped barrier region.

Effect of bexarotene on differentiation of glioblastoma multiforme compared with ATRA.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Since differentiation can attenuate or halt the growth of tumor cells, an image-based phenotypic screening was performed to find out drugs inducing morphological differentiation of GBMs. Bexarotene, a selective retinoid X receptor agonist, showed strong inhibition of neurospheroidal colony formation and migration of cultured primary GBM cells. Bexarotene treatment reduced nestin expression, while significantly increasing glial fibrillary acidic protein (GFAP) expression. The effect of bexarotene on gene expression profile was compared with the activity of all-trans retinoic acid (ATRA), a well-known differentiation inducer. Both drugs largely altered the gene expression pattern into a tumor-ameliorating direction. These drugs increased the gene expression levels of Krüppel-like factor 9 (KLF9), regulator of G-protein signaling 4 (RGS4), growth differentiation factor 15 (GDF15), angiopoietin-like protein 4 (ANGPTL4), and lowered the level of chemokine receptor type 4 (CXCR4). However, transglutaminase 2 (TG2) induction, an adverse effect of ATRA, was much weaker in bexarotene treated primary GBM cells. Consistently, the TG2 enzymatic activity was negligibly affected by bexarotene treatment. It is important to control TG2 overexpression since its upregulation is correlated with tumor transformation and drug resistance. Bexarotene also showed in vivo tumoricidal effects in a GBM xenograft mouse model. Therefore, we suggest bexarotene as a more beneficial differentiation agent than ATRA for GBM.

Effect of Exposure to Second-Hand Smoke on the Quality of Life: A Nationwide Population-Based Study from South Korea.

BACKGROUND: Although exposure to second-hand smoke (SHS) has been associated with various medical conditions, only limited data are available on its association with health-related quality of life (HRQOL), particularly data obtained with the EQ-5D or EQ visual analogue scale (VAS). METHODS: This cross-sectional study evaluated 10,532 adult never-smokers who participated in the fifth Korea National Health and Nutrition Examination Survey. By using linear regression models to adjust for possible confounders and incorporating survey weights in analyses, the association between exposure to SHS and HRQOL-measured with the EQ-5D index and the EQ-VAS score-was evaluated. Data were further stratified by the amount of exposure time. RESULTS: After weighted analysis and adjustment, exposure to SHS was significantly associated with lower measures on the EQ-5D index (ß = -0.007, P = 0.005) and EQ-VAS score (ß = -1.936, P < 0.001). When comparing the unexposed group with the groups exposed <2h/day and ≥2h/day, exposure to a longer duration of SHS was significantly associated with lower scores on the EQ-5D index and the EQ-VAS score. CONCLUSION: In conclusion, exposure to SHS was associated with reduced HRQOL measured by the EQ-5D index and EQ-VAS score, revealing a dose-response relationship.

Indatraline inhibits Rho- and calcium-mediated glioblastoma cell motility and angiogenesis.

Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor of the central nervous system (CNS). As an attempt to identify drugs for GBM therapeutics, phenotypic assays were used to screen 1000 chemicals from a clinical compound library. GBM subtypes exhibited different capabilities to induce angiogenesis when cultured on Matrigel; proneural cells migrated and formed a tube-like structure without endothelial cells. Among the compounds screened, indatraline, a nonselective monoamine transporter inhibitor, suppressed these morphological changes; it dose dependently inhibited cell spreading, migration, and in vitro/in vivo tube formation. In addition to intracellular calcium concentration, indatraline increased the level of Rho GTPase and its activity. Moreover, indatraline downregulated angiogenesis-related genes such as IGFBP2, PTN, VEGFA, PDGFRA, and VEGFR as well as nestin, a stem cell marker. These findings collectively suggest that the activation of Rho GTPase and the suppression of angiogenesis-related factors mediate the antiangiogenic activity of indatraline in proneural GBM culture.

Inhibition of c-Kit signaling by diosmetin isolated from Chrysanthemum morifolium.

The interaction of stem cell factor (SCF) with its cognate receptor c-Kit is closely associated with the survival and maturation of melanocytes. To investigate novel depigmentation agents, we screened 2,000 plant extracts for c-Kit inhibitors to identify active small molecules by using time-resolved fluorescence enzyme assays. For the active extracts identified as inhibitors of c-Kit enzyme, we evaluated the effects of the active extracts and isolated flavonoids on c-Kit phosphorylation in MO7e/melanocytes. Anti-melanogenic activity was also examined in melanocytes and melanoderm model. The flavonoids such as diosmetin, apigenin, acacetin and luteolin isolated from Chrysanthemum morifolium were found to be active in inhibiting c-Kit both at enzyme and cellular levels. In addition, these flavonoids attenuated SCF-induced proliferation of human primary melanocytes without toxicity and suppressed ultraviolet (UV) B irradiation-mediated melanin synthesis significantly. Among the active flavonoids, diosmetin was found to inhibit SCF-induced melanogenesis in a human melanoderm model. These results strongly suggest that C. morifolium extract and diosmetin have potential to suppress SCF-/UVB-induced melanogenesis, and could be developed as anti-pigmentation agents.

Prevalence and predictors of pulmonary embolism in Korean patients with exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Data concerning the rate of pulmonary embolism (PE) in Asian patients with chronic obstructive pulmonary disease (COPD) exacerbation are sparse, and no study has shown predictors of PE in these patients. OBJECTIVES: The purpose of the present study was to investigate the prevalence and predictors of PE in Korean patients with COPD exacerbation. METHODS: Hospitalized patients with COPD exacerbations were prospectively enrolled into this study and underwent computed tomography (CT) pulmonary angiography and indirect CT venography. RESULTS: The most common cause of COPD exacerbation was lower respiratory tract infection (82%; n = 84), followed by PE (5%; n = 5). Eight patients (8%) had venous thromboembolism, and deep vein thrombosis (DVT) was seen in 6%, with proximal DVT in 4%. On multivariate analysis, the absence of symptoms of respiratory infection and plasma D-dimer elevation (≥500 µg/l) were significant factors predicting PE in patients with COPD exacerbations (odds ratio 31, 95% confidence interval 2-563, p = 0.02, and odds ratio 25, 95% confidence interval 1-464, p = 0.03, respectively). CONCLUSIONS: PE comprises approximately 5% of the etiologies of COPD exacerbations in Koreans. The absence of symptoms suggestive of respiratory infection and elevated plasma D-dimer levels were significant predictors of PE in this population.

Clinical relevance and characteristics of pleural effusion in patients with Mycoplasma pneumoniae pneumonia.

Data regarding parapneumonic pleural effusion in Mycoplasma pneumoniae pneumonia (MP) patients are limited. In this study MP patients with pleural effusion tended to be younger and had longer hospital stays and more common use of systemic steroids compared to those without pleural effusion. In 5 of the 6 patients for whom pleural fluid data were available, the pleural effusion was lymphocyte-predominant rather than polymorphonuclear leukocyte-predominant; these patients also had elevated adenosine deaminase levels. Taken together, these results indicate that MP patients with pleural effusion may have a more severe form compared to those without pleural effusion. M. pneumoniae should be considered an aetiological agent of lymphocyte-predominant pleural effusion.

Clinical relevance of pulmonary infarction in patients with pulmonary embolism.

INTRODUCTION: Data regarding the clinical relevance of pulmonary infarction (PI) in patients with pulmonary embolism (PE) are lacking. The aim of this study was to investigate the clinical features of PE patients with PI and the prognostic role of PI for PE patients. MATERIALS AND METHODS: Based on computed tomography scan, 509 patients with PE were divided into two groups, the infarction group (n=45) and the non-infarction group (n=464). A variety of clinical parameters were compared between the two groups. RESULTS: In the infarction group, the largest pulmonary arteries involved by emboli were central rather than peripheral and more proximal as compared to the non-infarction group (p=0.01 and p<0.03, respectively). Thrombolytic agents tended to be more frequently administered in the infarction group (13.3% [n=6] versus 6.3% [n=29], p=0.07). In-hospital mortality, PE-related deaths, and the recurrence rate of PE did not differ between the two groups. CONCLUSIONS: The present study did not demonstrate that PI is a prognostic indicator of recurrence and mortality in PE patients. We suggest the possibility that blood clot burden is greater in PE patients with PI, although PI by itself occurs in small pulmonary arteries.

Replication of results of genome-wide association studies on lung cancer susceptibility loci in a Korean population.

BACKGROUND AND OBJECTIVE: Genome-wide association studies (GWAS) have identified the three chromosomal regions, 5p15, 6p21 and 15q25, as being associated with lung cancer risk in European populations. This study was performed to confirm these associations in Korean patients with lung cancer. METHODS: The genotypes at rs2736100, rs402710, rs401681 and rs31489 at 5p15, rs9295740 at 6p22, which is in extensive linkage disequilibrium with the 6p21 region, as well as rs2036534 and rs6495309 at 15q25, were determined in 1094 patients with lung cancer and 1100 healthy control subjects, who were frequency matched for age and gender. RESULTS: The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR 0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P = 0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309, aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung cancer risk. The magnitude of the effect was similar to that reported in previous studies, and the association was in the same direction. The effect of SNP in the 5p15 region on the risk of lung cancer was significant only for adenocarcinoma. The two SNP in the 15q25 region were significantly associated with lung cancer risk in ever-smokers and in patients with squamous-cell carcinoma. However, there was no association between the SNP at 6p22 and lung cancer risk. CONCLUSIONS: The association between SNP in the 5p15 and 15q25 regions and the risk of lung cancer was confirmed in a Korean population.

Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia.

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

AKT1 polymorphisms and survival of early stage non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: This study was conducted to investigate the impact of polymorphisms in the AKT1 gene on the survival of early stage non-small cell lung cancer (NSCLC) patients. METHODS: Three hundred and ten patients with surgically resected NSCLC were enrolled. The rs3803300, rs1130214, rs3730358, rs1130233, and rs2494732 single nucleotide polymorphisms (SNPs) in the AKT1 gene were investigated. The genotype and haplotype associations with overall survival (OS) and disease free survival (DFS) were analyzed. RESULTS: The three SNPs (rs3803300, rs1130214, and rs2494732) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased in a dose-dependent manner as the number of bad genotypes increased (P(trend) = <1.0 × 10(-4) and 0.001, respectively). Patients with 2 bad genotypes had a significantly worse OS and DFS compared with those with 0 bad genotypes (adjusted hazard ratio (HR) = 3.08, 95% confidence interval (CI) = 1.61-5.89, P = 0.001; and adjusted HR = 2.04, 95% CI = 1.22-3.43, P = 0.01). CONCLUSIONS: These results suggest that the AKT1 polymorphisms could be used as prognostic markers for the patients with early-stage NSCLC.

Performance of whole-blood interferon-gamma release assay in patients admitted to the emergency department with pulmonary infiltrates.

BACKGROUND: This study was conducted to evaluate the performance of a whole-blood interferon-gamma release assay in inpatients who were admitted to the emergency department (ED) with pulmonary infiltrates who required a differential diagnosis with pulmonary tuberculosis (TB). METHODS: The patients with pulmonary infiltrates who received a QuantiFERON (QFT) test in the ED were included as an inpatient group and were divided into TB and non-TB group based on the final diagnosis. Patients with pulmonary TB who were tested in the outpatient department served as a control group. RESULTS: In total, 377 QFT tests were analyzed. Of the 284 inpatient QFT tests, 29.6% had an indeterminate result (35.2% in the 196 patients with non-TB and 17.0% in the 88 patients with TB). In contrast, only 1.1% of the 93 outpatients with TB returned an indeterminate result (p<0.001). The indeterminate QFT results in the inpatient group were independently associated with lymphocytopenia, hypoalbuminemia, and high C-reactive protein levels. Non-positive QFT results in inpatients with TB were associated with lymphocytopenia and hypoalbuminemia, while non-positive QFT results in outpatients with TB were associated with high erythrocyte sedimentation rates and radiographically more severe diseases. CONCLUSIONS: QFT tests in ED-based inpatients with pulmonary infiltrate return indeterminate results relatively frequently. In addition, inpatients and outpatients with pulmonary TB may differ in terms of the risk factors on non-positive QFT results.

Adjunctive effects of cyclosporine and macrolide in rapidly progressive cryptogenic organizing pneumonia with no prompt response to steroid.

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. However, it can rapidly worsen and lead to respiratory failure that is refractory to corticosteroids. Adjunctive drugs have been used in refractory cases with various outcomes, but treatment experience is still lacking. We present a case of rapidly progressive COP accompanying air leak syndrome, which showed no prompt response to corticosteroids alone but gradual improvement with the addition of cyclosporine and macrolide. This case report supports the existing literature suggesting that an early therapeutic trial of this drug combination might be considered in COP patients whose condition worsens despite corticosteroid administration.

Dual roles of a variable number of tandem repeat polymorphism in the TERT gene in lung cancer.

This study was conducted to determine the impact of a functional tandem repeat minisatellite (MNS16A) polymorphism in the telomerase reverse transcriptase (TERT) gene on the risk of lung cancer, as well as on survival of patients with non-small-cell lung cancer (NSCLC). The effect of the MNS16A variable number of tandem repeat (VNTR) polymorphism on the risk of lung cancer was evaluated in a case-control study that consisted of 937 lung cancer patients and 943 healthy controls. The effect of the polymorphism on survival outcome was evaluated in 703 patients with surgically resected NSCLC. Compared with the VNTR-302 allele, the VNTR-243 allele was associated with a significantly increased risk of lung cancer (adjusted odds ratio, 1.55; 95% confidence interval [CI], 1.07-2.25; P = 0.02). In addition, the genotypes carrying at least one VNTR-243 allele were associated with a significantly increased risk of lung cancer compared with the genotypes with no VNTR-243 allele (adjusted odds ratio, 1.61; 95% CI, 1.09-2.38; P = 0.02). In contrast to the effect of the polymorphism on the risk of lung cancer, the genotypes carrying at least one VNTR-243 allele were associated with a significantly better overall survival in patients with surgically resected NSCLC (adjusted hazard ratio, 0.51; 95% CI, 0.28-0.93; P = 0.03). These findings suggest that the MNS16A VNTR polymorphism in the TERT gene has dual, conflicting roles in lung carcinogenesis. This polymorphism may increase the risk of lung cancer development, and may improve survival in lung cancer patients.

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers.

INTRODUCTION: Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in the development and progression of lung cancer. We searched for mutations of EGFR pathway genes in non-small cell lung cancers (NSCLCs) and analyzed their relationship with clinicopathologic features. METHODS: Mutations of EGFR, ERBB2, ERBB3, ERBB4, KRAS, NRAS, BRAF, PTEN, PIK3CA, LKB1, and AKT1 genes were determined by direct sequencing in 173 surgically resected NSCLCs--56 squamous cell carcinomas (SCCs) and 117 adenocarcinomas (ACs). RESULTS: Of the 173 NSCLCs, a total of 65 mutations were detected in 63 (36.4%) tumors--10 (17.9%) in SCCs and 53 (45.3%) in ACs. Mutations in EGFR pathway genes were significantly more frequent in women and ACs than in women and SCCs (p = 0.02 and p < 0.001, respectively). The mutations occurred in a mutually exclusive pattern. When the genes were divided into three subgroups according to their roles in the signaling cascade, mutations in the EGFR/ERBB2 and KRAS/BRAF genes were more frequent in ACs than in SCCs (p < 0.001 and p = 0.01, respectively). In marked contrast, mutations in the PIK3CA/PTEN were more frequent in SCCs than in ACs (p = 0.002). Furthermore, mutations in the PIK3CA/PTEN genes were more frequent in smokers (p = 0.04). DISCUSSION: Our study demonstrates that mutations in each part of the EGFR pathway were associated with different clinicopathologic features in patients with NSCLCs.

Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer.

This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non-small-cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty-eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease-free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P(trend) <0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS=3.53, 95% confidence interval [CI]=1.25-9.97, P=0.02, and aHR for DFS=3.31, 95% CI=1.41-7.76, P=0.006; and aHR for OS=5.47, 95% CI=1.87-16.00, P=0.002, and aHR for DFS=4.42, 95% CI=1.82-10.74, P=0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC.

Association of a common AGO1 variant with lung cancer risk: a two-stage case-control study.

Based on the important role of microRNA (miRNA) biosynthesis genes in carcinogenesis, we hypothesized that polymorphisms in the miRNA biosynthesis genes may modulate susceptibility to lung cancer. To test this hypothesis, we conducted a two-stage study to evaluate the associations between single nucleotide polymorphisms (SNPs) in the miRNA biosynthesis genes and the risk of lung cancer. In stage 1 of the study, 24 SNPs in the 11 miRNA biosynthesis genes (DROSHA, DGCR8, RAN, XPO5, DICER, AGO1, AGO2, HIWI, GEMIN3, GEMIN4, and TRBP) were genotyped in 100 lung cancer patients and 100 healthy controls using a sequenome mass spectrometry-based genotyping assay. One promising SNP (AGO1 rs636832A > G) was selected for stage 2 of the study, and genotyped by a melting-curve analysis using fluorescence-labeled hybridization probes in an independent set of 552 cases and 552 controls. The AGO1 rs636832A > G exhibited highly consistent results between the two stages of the study. In combined analysis, the 636832A > G was associated with a significantly decreased risk of lung cancer in a dose-dependent manner (P(trend) = 6.0 × 10(-4)). Individuals with at least one rs636832G allele were at a significantly decreased risk of lung cancer compared with those with the AA genotype (adjusted odds ratio = 0.67, 95% confidence interval = 0.53-0.84, P = 4.0 × 10(-4)). This finding suggests that the AGO1 rs636832A > G might be a useful marker for determining the susceptibility to lung cancer and that the AGO1 gene might be involved in the development of lung cancer.

The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Polymorphisms in the caspase genes and the risk of lung cancer.

INTRODUCTION: Caspases (CASPs) are important regulators and executioners in apoptosis pathway and play a crucial role in the development and progression of cancer. On the basis of the interactions of CASPs in the apoptotic pathway, we evaluated the association between 11 polymorphisms of CASP3, 6, 7, 8, 9, and 10 genes and the risk of lung cancer. METHODS: The genotypes were determined in 720 patients with lung cancer and 720 healthy controls frequency matched for age and gender. RESULTS: In individual polymorphism analysis, the CASP7 rs2227310C>G and CASP9 rs4645981C>T were associated with 1.40-fold and 1.28-fold increased risk of lung cancer under recessive and dominant models for the variant allele of each polymorphism, respectively. In the case of the CASP3 77G>A, subjects with the GG genotype were at a 1.19-fold increased risk of lung cancer compared with those with at least one variant allele. When the three polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of risk genotypes increased (ptrend <0.001). Subjects with two and three risk genotypes carried a significantly increased risk of lung cancer compared with those with zero risk genotype (adjusted odds ratio = 1.56, 95% confidence interval = 1.14-2.13, p = 0.005 and adjusted odds ratio = 2.54, 95% confidence interval = 1.28-5.02, p = 0.008, respectively). CONCLUSIONS: These results suggest that a combined analysis of these three CASP gene polymorphisms might better predict the risk of lung cancer than analysis of a single polymorphism.