Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.

Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19×10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.

[Effect of ursolic acid on caspase-3 and PARP expression of human MCF-7 cells].

OBJECTIVE: To study the effect of ursolic acid (UA), apentacyclic triterpene acid, on MCF-7 cell apoptosis, and probable mechanism involved by detecting the expressions of caspase-3 and poly ADP-ribose polymerase(PARP) at protein level. METHOD: MCF-7 cells were cultured with different concentrations of UA. Growth inhibition of UA on MCF-7 cells was evaluated by MTT assay. Cell cycle and sub-G1 peak were performed by FCM. Morphologic changes of UA-treated cells were observed by light microscope. Apoptotic cells with condensed or fragmented nuclei were visualized by Ho 33258 staining by a fluorescence microscope (EX: U. V.). The protein expression of caspase-3 and PARP was analyzed by immunofluorescence cell staining (SABC-Cy3). RESULT: 24 hours after UA treatment, inhibition of MCF-7 cell growth was concentration-dependent. The IC50 value for UA was (22.6 +/- 3.0) micromo x L(-1). Cell cycle anaysis by FCM showed that 50 micromol x L(-1) of UA arrested MCF-7 cell cycle at G0 - G1 phase. Morphological changes of MCF-7 Cells exhibited many of the hallmark features of apoptosis, including chromatin clumps and aggregation and DNA fragmentation. UA increased caspase-3 protein expression. CONCLUSION: The results suggest that UA evokes MCF-7 cell apoptosis is correlation with the up-regulation of caspase-3. Our study indicated that UA might be a potential Chinese medical component for breast neoplasm.

[Study on gene expression pattern in 16HBE cells treated with NiS].

BACKGROUND: Recent researches have found that NiS can cause the malignant transforming activity and carcinogenicity on human bronchial epithelial cells (16HBE). Its molecular mechanism may be involved in mutation of genes and abnormal expression of transcription factors on 16HBE. And so, this study takes advantage of a model of 16HBE transformed by NiS and screens the differentially expressed genes between 16HBE cells and NiS treated 16HBE cells (NiS-16HBE) using cDNA microarray. METHODS: The total RNA was extracted from 16HBE cells and NiS-16HBE cells. The cDNA probes were prepared by labeling with Cy3-dCTP and Cy5-dCTP respectively through reverse transcription. The mixed probes were then hybridized to the cDNA microarray chips containing 4000 human genes. The chips were scanned by ScanArray 4000 laser scanner. The acquired fluorescent signals were analyzed by GenPix Pro 3.0 software. Bioinformation function of those differentially expressed genes was analysed. RESULTS: A total of 151 genes exhibited differential expression between 16HBE cells and NiS-16HBE cells. The expression of 70 genes ( 46.36%) was down-regulated and that of 81 genes (53.64%) was up-regulated. CONCLUSIONS: The regulation of genes including stress response genes, immune related genes, DNA synthesis and repair genes, metabolism genes, pro-oncogenes and tumor suppressor genes may be involved in transforming activity of NiS.

Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.

To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.

[A study on the methodology regarding the prevalence survey of chronic obstructive pulmonary disease in China].

OBJECTIVE: To explore the methodology on prevalence study of chronic obstructive pulmonary disease (COPD) in line with the world, to obtain accurate epidemic data of COPD in China. METHODS: A national multi-center cross-sectional survey on prevalence, risk factors and burden of COPD was conducted in China. In each area, a population-based cluster sample of approximately 1450 individuals aged 40 years or older was interviewed, using standardized questionnaires that were revised on the methodology of burden of lung diseases (BOLD) study and according under the context of China. All participants were submitted to pre-bronchodilator spirometry. Those with airflow limitation received post-bronchodilator spirometry, physical examination, X-rays of chest and EKG (electrocardiogram) tests. The post-bronchodialators FEV1/FVC < 70% was identified as having COPD. RESULTS: Investigation has been completed with the same standardized procedures by all sites, up to the requirement of quality control. Over 85.0% of the spirometry tests and 95.0% of questionnaires had met the criteria of quality control in each area. Overall, 95.2% of the data was valid with acceptable spirometry and questionaire, and the valid response rate was 79.0%. CONCLUSION: The protocol was in line with the international standards, by which the prevalence of COPD in China was of adequate quality and valid.