Lung Cancer In Chinese Population Research Articles

Functional polymorphisms on chromosome 5p15.33 disturb telomere biology and confer the risk of non-small cell lung cancer in Chinese population.

The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer. However, causal variants in this region have not been fully uncovered. In this study, we intended to identify functional polymorphisms associated with non-small cell lung cancer (NSCLC) susceptibility in Chinese population. A targeted sequencing on 5p15.33 region was conducted in 400 NSCLC cases. We selected candidate variants by comparing genotypic frequency with data from 1000 Genomes Project, and their associations with NSCLC were validated in 985 cases and 970 controls. The relationships between risk variants and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays (EMSA) were performed to explore potential functions and reveal carcinogenic mechanisms. As a result, we identified 1478 variants through targeted sequencing and selected 17 candidates. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95%CI: 1.18-1.52, P = 7.78 × 10-6 ), rs10054203 (OR = 1.29, 95%CI: 1.13-1.46, P = 1.37 × 10-4 ), rs2736107 (OR = 1.28, 95%CI: 1.11-1.47, P = 5.14 × 10-4 ), and rs2853677 (OR = 1.23, 95%CI: 1.08-1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Mechanistically, the rs7726159-A increased TERT transcription through mediating allele-specific MYC binding. In conclusion, the functional variant rs7726159 confers lung cancer susceptibility might by affecting MYC binding and inducing telomere lengthening, which provides a new insight into the crucial role of telomere biology in tumorigenesis.

Single nucleotide polymorphism in the 3\u2032 untranslated region of LPP is a risk factor for lung cancer: a case-control study

BackgroundSingle nucleotide polymorphisms (SNPs) in 3′-untranslated region (UTR) of genes related with cell-matrix adhesions and migration might affect miRNA binding and potentially affect the risk of cancer. The present study aimed to screen SNPs in 3′ UTR of cancer-related genes and investigate their contribution to the susceptibility of lung cancer.MethodsSeven SNPs were selected and genotyped in a case-control study (322 lung cancer patients and 384 controls) among Chinese Han population. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender in multiple genetic models.ResultsIn stratified analyses by gender, three (rs1064607, rs3796283 and rs2378456) of LPP gene were associated with a significantly increased susceptibility for lung cancer among male population. Besides, LPP rs2378456 weakened lung cancer risk in female. LPP rs1064607 polymorphism was significantly correlated with increased risk of lung adenocarcinoma. Furthermore, AA genotype of TNS3 rs9876 polymorphism was associated with lymphatic metastasis.ConclusionOur results provides evidence for the impact of LPP polymorphisms on the susceptibility to lung cancer in Chinese population.

Methods of computed tomography screening and management of lung cancer in Tianjin: design of a population-based cohort study.

ObjectiveEuropean lung cancer screening studies using computed tomography (CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time (VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.MethodsThis study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol (Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT (a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.ResultsThe diagnostic performance of volume- and diameter-based management for lung nodules in a Chinese population will be estimated and compared.ConclusionsThrough the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.

Correlation Between Serum Estradiol and Lung Cancer in Chinese Population

To analyze the correlation between the serum estradiol and lung cancer in Chinese population, PubMed, the Cochrane database and the China National Knowledge Internet database as well as VIP, WANGFANG MED, Sino Med were comprehensively searched for related studies strictly according to the selection criteria. Statistical analysis was performed using Review Manager 5.3 software. 16 studies were included for analysis, of which there were 736 subjects in the lung cancer group, 544 ones in the healthy control group. The results of Meta-analysis showed that the serum estradiol levels were higher in the lung cancer group than in the control one (SMD=0.81, 95%CI 0.31-1.30, Z=3.20, P 0.05) compared to the healthy control groups. Therefore, the serum estradiol level in the patients with lung cancer is higher than that in the healthy control population, suggesting serum estradiol level may be associated with the pathogenesis of lung cancer and expected to become a marker for the diagnosis of lung cancer, especially in Chinese population.

Functional Polymorphisms on Chromosome 5p15.33 Disturb Telomere Biology and Confer the Risk of Non-Small Cell Lung Cancer in Chinese Population

Background: The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer, but causal variants have not been fully investigated. We intended to explore functional polymorphisms associated with non-small cell lung cancer (NSCLC) susceptibility and their relationship with telomere length in Chinese population. Methods: We conducted a targeted sequencing at 5p15.33 with 400 patients. Comparing with genotypic frequency in 1000 Genomes Project, we selected candidate variants and validated their associations with NSCLC in 985 cases and 970 controls. The relationships between susceptibility SNPs and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays were performed to reveal potential mechanisms. Findings: we identified 1478 variants through targeted sequencing and selected 17 candidate variants. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95% CI: 1.18-1.52, P = 7.78 × 10-6 )，rs10054203 (OR = 1.29, 95% CI: 1.13-1.46, P = 1.37 × 10-4 )，rs2736107 (OR = 1.28, 95% CI: 1.11-1.47, P = 5.14 × 10-4 ) and rs2853677 (OR = 1.23, 95% CI: 1.08-1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Functional exploration characterized rs7726159 promoted TERT transcription through disrupting transcription factor binding. Interpretation: The functional polymorphism, rs7726159, confers lung cancer susceptibility by disturbing telomere biology. Our study illustrated the functional significance of this variant in lung cancer initiation, which provides a new insight into the important role of telomere dysfunction in tumor progression. Funding Statement: This work was supported by the National Natural Science Foundation of China (81572071). Declaration of Interests: The authors declare that they have no potential conflicts of interest. Ethics Approval Statement: Written informed consent was obtained from each individual, and this study was approved by the Institutional Review Board of the Tongji Medical College, HUST.

Polymorphism rs3819102 in thymidylate synthase and environmental factors: effects on lung cancer in Chinese population

PurposeLung cancer is the leading cause of cancer death worldwide, and the predominant risk factor for its development is smoking. Thymidylate synthase (TYMS) is a key enzyme in DNA synthesis that catalyzes the conversion of deoxyuridine monophosphate to dTMP. Rs931794, a single nucleotide polymorphism located in the TYMS gene, was suggested to be associated with cancer risk. MethodsTo analyze the interaction between rs3819102 and environmental factors on the risk of lung cancer in a Chinese population, single nucleotide polymorphismscan was used to genotype this polymorphism in 974 lung cancer cases and 1005 control subjects. ResultsThe frequencies of TT, CT, and CC genotypes of TYMS rs3819102 were 61.8%, 32.9%, and 5.3% in controls, and 53.8%, 38.4%, and 7.8% in cases, respectively. Compared with the TT genotype, the CT (odds ratio [OR], 1.380; 95% confidence interval [CI], 1.131-1.683), and CC (OR, 1.786; 95% CI, 1.213-2.644) genotypes were associated with an increased risk of lung cancer after adjustment for age, gender, smoking status, and family history. The C allele of rs3819102 is the risk allele for lung carcinogenesis in a dominant model (OR, 1.435; 95% CI, 1.188-1.735). In a stratified analysis, the risk effects of both the CT and CC genotypes of rs3819102 were more evident in subgroups of smokers and people without a family history of cancer. ConclusionThe rs3819102 polymorphism in TYMS might increase susceptibility to environmental factors and contribute to the risk of lung cancer. The C allele is a risk allele in lung carcinogenesis.

The DNMT3B -579G>T Polymorphism Is Significantly Associated With the Risk of Gastric Cancer but not Lung Cancer in Chinese Population.

The -149C>T and -579G>T, 2 single nucleotide polymorphisms in de novo methyltransferase 3B gene promoter, have been previously reported to potentially alter the promoter activity and to influence cancer risk. However, the results from previous studies remain conflicting rather than conclusive. In view of this, we conducted a case–control study and then a meta-analysis to examine the association between these 2 single-nucleotide polymorphisms with risk of lung and gastric cancer in Chinese population. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. In this case–control study, no significant association with lung or gastric cancer risk was observed for -149C>T, while -579G>T was significantly correlated with the risk of gastric cancer but not lung cancer. Moreover, haplotype analysis showed that haplotype -149T/-579 T, which carried the risk -579 T allele, significantly increased the susceptibility to gastric cancer. However, none of the haplotypes was associated with the risk of lung cancer. The following meta-analysis involved only Chinese population and further confirmed the significant association of -579G>T with gastric cancer but not lung cancer and suggested no significant association between -149C>T and risk of lung or gastric cancer. Collectively, DNMT3B -579G>T polymorphism is associated with gastric cancer risk in Chinese population, and the -579G>T may be used as a genetic biomarker to predict the risk of gastric cancer in Chinese population.

Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis.

BackgroundTo explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis.Materials and Methods480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival.ResultsG-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results.ConclusionsThe two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs.

Genetic susceptibility of lung cancer in Chinese population: An overview of systematic reviews and meta-analyses.

Genetic susceptibility of lung cancer has been widely studied for Chinese population, and meta-analysis of candidate gene association studies has also been performed for those genes. However, the overall evidence has not been well recognized. To investigate genetic association for the risk of lung cancer in Chinese. An overview of systematic reviews and meta-analyses of candidate gene association studies for lung cancer in Chinese was performed up to August 10th , 2016. The AMSTAR tool was used to assess the quality of the included systematic reviews and meta-analyses. Bibliometric analysis was performed to analyze the characteristics of reviews. A total of 21 variants in 17 genes from 20 meta-analyses were included in this study. All 20 meta-analyses were published from 2011 to 2016. The quality scores of AMSTAR ranged from 3 to 7. All included genes were in the pathogenesis of lung cancer, such as the CYPs genes, GSTs genes, and base excision repair genes. Three polymorphisms were found to be associated with decreased risk of lung cancer for Chinese, 15 polymorphisms were found to be associated with increased risk of lung cancer for Chinese, but three polymorphisms were found to be not associated with lung cancer risk for Chinese. The current study supports the genetic risk factors of lung cancer for Chinese are more likely to be variants from genes that contribute to the etiology of lung cancer.

Ataxia Telangiectasia-Mutated (ATM)Polymorphisms and Risk of Lung Cancer in a Chinese Population.

The ataxia telangiectasia-mutated (ATM) gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs) with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer. A population-based case-control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR) and 95% confidence intervals (CIs). Adjusted models controlled for age, sex, and smoking status. The study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06-2.35) and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08-2.08) in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT), ATMrs228589 (AA), and p53rs1042522 (CC) concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43-9.45) of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer. This study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples.

Clinicopathological significance of p14ARF expression in lung cancer: a meta-analysis.

Backgroundp14ARF, a tumor suppressor protein, encoded by the p16 tumor suppressor gene, has been reported to be associated with the clinicopathological features of lung cancer. However, the evaluated outcomes were inconsistent and remained inconclusive. In this study, we conducted a meta-analysis to clarify the significance of p14ARF expression in lung cancer pathogenesis.Materials and methodsElectronic databases, PubMed, Web of Knowledge, Embase, and CNKI, were retrieved to collect relevant articles with inclusion and exclusion criteria. Using Stata 12.0 software, 95% confidence intervals (CIs) and odds ratios (ORs) were calculated.ResultsA total of 15 eligible case–control studies that evaluated the relationship between p14ARF expression and lung cancer were included in the meta-analysis. The results demonstrated that there were significant associations between p14ARF expression and the risk of non-small-cell lung cancer (NSCLC), lung adenocarcinoma, and lung squamous carcinoma (for NSCLC, OR =11.02, 95% CI =5.30–22.92; for lung adenocarcinoma, OR =7.28, 95% CI =3.92–13.50; and for lung squamous carcinoma, OR =14.40, 95% CI =2.83–73.24). In the stratified analysis based on race, significant associations between p14ARF expression and lung cancer risk were found in Chinese population and Caucasians (for Chinese population, OR = 7.02, 95% CI =4.48–11.00 and for Caucasians, OR =4.19, 95% CI =1.42–12.38). Furthermore, the expression of p14ARF was significantly associated with the TNM-stage of lung cancer in Chinese population (OR =2.07, 95% CI =1.38–3.10).Conclusionp14ARF expression was significantly associated with the risk of lung cancer. In addition, the data of the meta-analysis showed that there was a significant correlation between p14ARF expression and the TNM-stage of lung cancer in Chinese population.

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in Chinese population: A retrospective study.

ObjectivesTo evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC).ResultsAll patients completed definitive radiotherapy and 74 (85.1%) patients administrated platinum-based chemotherapy. The median radiation dose was 50.4Gy to PTV and 64.4 Gy simultaneously to the PGTV. The overall response rate (ORR) was 57.5% (50/87). The median duration of follow up was 24.6 months. The 1, 2, 3-year local control rate was 79.0%, 66.1%, and 60.5%, respectively. The 1, 2, 3-year overall survival (OS) rate was 89.7%, 56.7%, and 30.6%, respectively. Subgroup analysis showed that the median OS in concurrent chemoradiation (CCRT) was much better than non-CCRT (35.7 vs. 26.4 months) (HR: 0.52, 95% CI: 0.32–0.95, P = 0.033). Twenty-two (25.3%) patients experienced acute grade 3 esophagitis and 10 (11.5%) experienced acute grade ≥ 3 radiation pneumonitis. There were 2 (2.6%) late grade 3 pulmonary toxicity and no late grade ≥ 3 esophageal toxicity was observed.Materials and MethodsA total of 87 patients with locally advanced NSCLC who received SIB-IMRT from Jan. 2009 to Dec. 2012 in our hospital were retrospectively analyzed. Male accounted for 88.5%, with a median age of 61 years old. The SIB-IMRT plans were designed to deliver 50.4–64.0 Gy in 28–33 fractions (1.8–2.1 Gy/fraction) to PTV while simultaneously delivering 60.0–74.3 Gy in 28–33 fractions (2.0–2.5 Gy/fraction) to PGTV.ConclusionsSIB-IMRT, especially with concurrent chemotherapy, appears to be an effective and safe option to treat patients with locally advanced NSCLC. More prospective clinical studies should be warranted.

Genetic Polymorphisms in the Apoptosis-Associated Gene CASP3 and the Risk of Lung Cancer in Chinese Population

Caspase-3 (CASP3) plays a central role in executing cell apoptosis and thus in carcinogenesis. We previously investigated the relationship between functional polymorphisms in CAPS3 829 A>C and 20541 C>T and risk of esophageal squamous cell carcinoma. However little is known about the role of CASP3 variants in susceptibility to lung cancer. To figure out the contribution of CASP3 polymorphisms to lung cancer risk, genotypes of 1000 lung cancer patients and 1000 controls were conducted by RFLP-PCR (restriction fragment length polymorphism PCR). The transcriptional activity of CASP3 829 A>C was examined by dual luciferase reporter assay. Logistic regression was applied to calculate Odds ratios (OR) and 95% confidence intervals (95%CI). Compared with CASP3 829 AA genotype, AC and CC genotype had significantly increased risk of lung cancer with OR (95% CI) of 1.33 (1.09–1.63) and 1.55 (1.19–2.01), respectively. To further explore the possible impact of 829 A>C SNP on CASP3 transcriptional activity, we detected the dual luciferase activity of PGL3-promoter vectors containing 829A or 829C alleles in lung cancer cell lines and found that report gene expressions driven by 829A containing CASP3 promoter were 1.64-fold, 1.94-fold greater than those driven by CASP3 829C containing counterparts in A549 and NCI-H1975 cells (P<0.001). When stratified by sex, the significantly increased risk associated with CASP3 829 AC or CC genotype was obviousl in males with OR (95% CI) of 1.42 (1.11–1.81) and 1.51 (1.11–2.05), but not in females. When stratified by age, we found that CASP3 829 AC or CC genotype contributed to the risk of lung cancer in youngers with OR (95% CI) of 2.73 (1.71–4.34) and 4.02 (2.20–7.32), but not in elder group. We also found that 829AC or 829CC genotype increased adenocarcinoma risk compared with the AA genotype with OR (95%CI) of 1.33 (1.04–1.70) and 1.51(1.09–2.07). CASP3 polymorphism and smoking interaction was demonstrated related with higher risk of lung cancer. We achieved that the CASP3 829AC or 829CC genotypes was associated with increased risk of lung cancer in both non-smoker and smoker group, with OR (95%CI) of 1.48 (1.08–2.02) and OR (95%CI) of 1.64 (1.09–2.48) among non-smokers and OR (95%CI) of 2.68 (1.89–3.81) and OR (95%CI) of 3.23 (2.21–4.92) among smokers, respectively. Among carriers with 20541CT genotype, the ORs (95%CI) of risk with lung cancer for smoking <16, 16–28, or > 28 pack-years were 1.16(0.65–2.07), 1.66(0.98–2.82) and 5.01(3.31–7.58) compared with the 20541CC carriers. And among carriers with 20541CT genotype, the ORs (95%CI) were 0.86(0.33–2.20), 2.12(0.83–5.41) and 5.71(2.68–12.16). These results highlight apoptosis-related CASP3 as an important gene in human carcinogenesis and further support the CASP3 polymorphisms confer to the lung cancer susceptibility.

Identification of TRPCs genetic variants that modify risk for lung cancer based on the pathway and two-stage study

ObjectiveStore operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca2+ concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. MethodsWe identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform. ResultsWe found consistently significant associations of TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of sources of populations (additive model in combined population: adjusted OR=1.33, 95% CI=1.11–1.59 for rs9547991; adjusted OR=1.21, 95% CI=1.08–1.35 for rs978156; and adjusted OR=1.28, 95% CI=1.10–1.47 for rs11748198). When combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156, subjects carrying “≥1” variant alleles had a 1.29-fold increased risk of lung cancer (95% CI=1.15–1.46), compared with those carrying “0” variant allele. Lung cancer risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend=7.2×10−7). ConclusionThese findings suggested that TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese population. Our study provides the epidemiological evidence supporting a connection between TRPC members and lung cancer risks.

Preliminary analysis of genomic profiling of small cell lung cancer in Chinese population revealed frequent PIK3CA hotspot mutations.

e20089Background: There are currently no targeted agents available for treating small cell lung cancers (SCLC). Recent genomic studies on SCLC in western population have shown that molecular altera...

Polymorphisms of the Stem Cell Marker Gene CD133 and the Risk of Lung Cancer in Chinese Population.

To explore the association of functional single-nucleotide polymorphisms (SNPs) of CD133 with the risk of lung cancer. We conducted a hospital-based, case-control study of 1017 lung cancer patients and 1035 cancer-free controls frequency-matched by age and sex. Four functional CD133 SNPs (rs2240688 A>C, rs10022537 T>A, rs7686732 C>G, and rs3130 C>T) were selected and genotyped. Unconditional univariate and multivariate logistic regression analyses were carried out to evaluate the associations of genotypes of CD133 SNPs with lung cancer risk. Compared with rs2240688 AA genotype, the variant AC/CC genotypes were associated with a statistically increased risk of lung cancer under a recessive model (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.42). The risk remained in patients with other histology types, but not with adenocarcinoma and squamous cell cancers. These findings suggest that SNP rs2240688 A>C of CD133 may be a potential biomarker for genetic susceptibility to lung cancer, but require further research with larger populations.

Plasma 25-hydroxyvitamin D deficiency is associated with the risk of non-small cell lung cancer in a Chinese population.

The association between vitamin D levels and lung cancer risk varies among distinct demographic populations; however, whether vitamin D levels are related to the risk of lung cancer in Chinese population is unknown. We aimed to elucidate the association of plasma 25-hydroxyvitamin D [25(OH)D] level with the risk of non-small cell lung cancer (NSCLC) in a Chinese population. A total of 100 NSCLC patients and, 100 age-, gender-, blood-collection-season- and resident area-matched, cancer-free controls were recruited. Plasma 25(OH)D2 and 25(OH)D3 levels were measured by LC/MS/MS mass spectrometry and HPLC. A logistic regression model was applied to estimate the association between 25(OH)D concentrations and NSCLC risk. Multivariable analysis showed that smoking history, and 25(OH)D deficiency (< 20 ng/mL) were related to a higher risk of NSCLC (P = 0.03). In addition, late stage (stage IIIB-IV) NSCLC was associated with lower 25(OH)D levels, as indicated by univariate analysis. Similarly, multivariate analysis showed that late stage (IIIB-IV) NSCLC was related to 25(OH)D deficiency. Plasma 25(OH)D deficiency is significantly associated with a higher risk of NSCLC, specifically late stage NSCLC.

IL-17A and IL-17F single nucleotide polymorphisms associated with lung cancer in Chinese population.

Genetic predisposition and environmental factors impact the development of lung cancer. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of the IL-17A and IL-17F genes with lung cancer risk in Chinese Han population. A total of 678 subjects were enrolled, including 320 lung cancer patients and 358 healthy controls. Six SNPs of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17F (rs763780, rs1266828 and rs12203582) were genotyped using the polymerase chain reaction (PCR) and ligase detection reaction (LDR). The distribution of IL-17A alleles and A and AA genotype for rs2275913 had a significant association with lung cancer risk (OR: 1.26, 95% confidence interval = 1.01-1.56 and OR: 2.08, 95% confidence interval = 1.311-3.31, respectively). In the subgroup analysis, people carrying homozygous variants of rs2275913 and rs12203582 were more likely to develop lung cancer both in adenocarcinoma (OR: 2.33, 95% confidence interval = 1.34-4.05; OR: 1.84, 95% confidence interval = 1.04-3.25) and advanced (OR: 2.35, 95% confidence interval = 1.46-3.80; OR: 1.74, 95% confidence interval = 1.06-2.87) groups. Although no interaction was found between variants of rs2275913 and rs12203582 and tobacco smoking (P > 0.05), smokers carrying homozygous variants of rs2275913 and rs12203582 are at high risk of lung cancer, while no relationship were found among non-smokers. No significant associations between rs3748067, rs3819025, rs763780 and rs1266828 polymorphisms and lung cancer risk were observed. Polymorphisms of both IL-17A and IL-17F may increase lung cancer risk in Chinese population, and are associated differently with subtypes of clinical-pathologic features and tobacco smoking history of lung cancer patients. SNPs of IL-17A and IL-17F predict lung cancer risk.

Polymorphisms in alternative splicing associated genes are associated with lung cancer risk in a Chinese population.

Alternative splicing is an important biological step during mRNA processing. Misregulation of alternative splicing can produce aberrant protein isoforms, thus contributing to cancer. We hypothesized that variants in 5 critical splicing factor-associated genes might play an important role in carcinogenesis of lung cancer. A case-control study including 1,341 non-small cell lung cancer (NSCLC) cases and 1,982 cancer-free controls were conducted to evaluate the associations of 16 tagging/functional polymorphisms in 5 splicing factor-associated genes with lung cancer risk. We found altogether 8 SNPs were associated with lung cancer risk with adjustment of age, gender, and smoking status after multiple corrections (FDR). Among these, six SNPs were related with SRSF7(rs10197412, OR (95% CI)=1.23 (1.06-1.43), P for FDR=0.018; rs12621103, OR(95% CI)=1.25 (1.08-1.46), P for FDR=0.016; rs13024811, OR (95% CI)=1.25 (1.07-1.46), P for FDR=0.016; rs2037875, OR (95% CI)=1.23 (1.06-1.42), P for FDR=0.018; rs3134628, OR (95% CI)=1.25(1.07-1.45), P for FDR=0.016 and rs6715866, OR (95% CI)=1.23 (1.07-1.43), P for FDR=0.016); one SNP was near PTBP2 (rs12566237: OR (95% CI)=1.16 (1.05-1.28), P for FDR=0.016) and one SNP in HNRNPQ (rs16876385: OR (95% CI)=1.17 (1.04-1.32), P for FDR=0.022). Our findings indicated that genetic variants in these splicing-associated genes might modify individual susceptibility to lung cancer in Chinese population. Further large-scale well-formed population studies and functional researches are warranted to confirm our findings.

Validation of autoantibody panel for early detection of lung cancer in Chinese population.

e22143 Background: Autoantibodies is an attractive diagnostic approach for early detection of malignant tumors. Our previous studies found a panel of 7 TAAs(p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2,...