Huan Guo

Publications (31)246.21 Total impact

• Article: Imputation-based association analyses identify new lung cancer susceptibility variants in CDK6 and SH3RF1 and their interactions with smoking in Chinese populations.

  Qifei Deng, Huan Guo, Juncheng Dai, Lei Yang, Chen Wu, Qing Wang, Zhibin Hu, Ming Yang, Li Liu, Dianke Yu, [......], Jing Feng, Kai Teng, Jianhang Gong, Chongqi Sun, Xiaoyan Hu, Kai Zhang, Jiachun Lu, Dongxin Lin, Hongbing Shen, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: Cell cycle regulation, apoptosis, oxidative stress, and inflammation response play critical roles in the development of smoking-induced lung cancer. However, it is still not well known whether their genetic variants are associated with lung cancer susceptibility. Here we performed imputation-based association analyses to investigate the influence of common genetic variants in these pathways and their interactions with smoking on lung cancer susceptibility. We first selected 24 042 unvalidated genetic variants in 798 genes from the imputed dataset of the previous lung cancer genome-wide association study (GWAS) in 2331 cases and 3077 controls, and then conducted additional two-stage validations in 4133 cases and 4522 controls. We found a genome-wide significant (P < 5.0×10(-8)) association for rs2282987 in CDK6 at 7q21.2 [odds ratio (OR) = 1.18, combined Padd = 2.27×10(-9)] and a consistent association for rs2706748 in SH3RF1 at 4q32.3 (OR = 1.17, combined Padd = 5.10×10(-6)). Interaction analyses showed that rs2282987 and rs2706748 interacted with both smoking status (Pinteraction were 1.04×10(-2) and 3.03×10(-2), respectively) and smoking dose (Pinteraction were 1.21×10(-2) and 5.21×10(-2), respectively) to contribute to lung cancer susceptibility in subjects aged 50 to 60 years. These results further underscore the contribution of genetic variants involved in pathways of cell cycle regulation and apoptosis to lung cancer susceptibility, and highlight gene-environment interactions in lung cancer etiology, especially in subjects aged 50 to 60 years.
  Carcinogenesis 05/2013; · 5.70 Impact Factor
• Article: A Genome-Wide Association Study for Serum Bilirubin Levels and Gene-Environment Interaction in a Chinese Population.

  Xiayun Dai, Chen Wu, Yunfeng He, Lixuan Gui, Li Zhou, Huan Guo, Jing Yuan, Binyao Yang, Jun Li, Qifei Deng, [......], Die Hu, Jiang Zhu, Xinwen Min, Mingjian Lang, Dongfeng Li, Handong Yang, Frank B Hu, Dongxin Lin, Tangchun Wu, Meian He
  [show abstract] [hide abstract]
  ABSTRACT: Bilirubin is an effective antioxidant and is influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified multiple loci affecting serum total bilirubin levels. However, most of the studies were conducted in European populations and little attention has been devoted either to genetic variants associated with direct and indirect bilirubin levels or to the gene-environment interactions on bilirubin levels. In this study, a two-stage GWAS was performed to identify genetic variants associated with all types of bilirubin levels in 10,282 Han Chinese individuals. Gene-environment interactions were further examined. Briefly, two previously reported loci, UGT1A1 on 2q37 (rs6742078 and rs4148323, combined P = 1.44 × 10(-89) and P = 5.05 × 10(-69) , respectively) and SLCO1B3 on 12p12 (rs2417940, combined P = 6.93 × 10(-19) ) were successfully replicated. The two loci explained 9.2% and 0.9% of the total variations of total bilirubin levels, respectively. Ethnic genetic differences were observed between Chinese and European populations. More importantly, a significant interaction was found between rs2417940 in SLCO1B3 gene and smoking on total bilirubin levels (P = 1.99 × 10(-3) ). Single nucleotide polymorphism (SNP) rs2417940 had stronger effects on total bilirubin levels in nonsmokers than in smokers, suggesting that the effects of SLCO1B3 genotype on bilirubin levels were partly dependent on smoking status. Consistent associations and interactions were observed for serum direct and indirect bilirubin levels.
  Genetic Epidemiology 01/2013; · 3.44 Impact Factor
• Article: A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk.

  Meian He, Chen Wu, Jianfeng Xu, Huan Guo, Handong Yang, Xiaomin Zhang, Jielin Sun, Dianke Yu, Li Zhou, Tao Peng, [......], Weimin Fang, Yuan Liang, Yun Zhai, Weihong Chen, Xiaoping Miao, Gangqiao Zhou, Frank B Hu, Dongxin Lin, Zengnan Mo, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers. DESIGN: We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls). RESULTS: The analyses showed association peaks on three genetic loci for CA19-9 (FUT6-FUT3 at 19p13.3, FUT2-CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16×10(-13)-3.30×10(-290)); four for CEA (ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33×10(-22)-5.81×10(-209)); and two for AFP (AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27×10(-18) and 1.28×10(-14)). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p<0.05). CONCLUSIONS: This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.
  Gut 01/2013; · 10.11 Impact Factor
• Article: Different physical activity subtypes and risk of metabolic syndrome in middle-aged and older chinese people.

  Mu Chen, Meian He, Xinwen Min, An Pan, Xiaomin Zhang, Ping Yao, Xiulou Li, Yuewei Liu, Jing Yuan, Weihong Chen, [......], Yuan Liang, Youjie Wang, Xiaoping Miao, Mingjian Lang, Peng Zhang, Dongfeng Li, Huan Guo, Handong Yang, Frank B Hu, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: The prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS. A total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66-0.86, P<0.001]. Compared with non-exercisers in a specific exercise type, jogging (OR 0.82, 95% CI 0.68-1.00, P = 0.046), tai chi (OR 0.72, 95% CI 0.60-0.88, P<0.001), and dancing (OR 0.56, 95% CI 0.47-0.67, P<0.001) were associated with significantly lower odds of MetS. Furthermore, each 1-h/week increment in tai chi and dancing was associated with a 5% (95% CI 2%-9%) and a 9% (95% CI 6%, 12%) lower risk of MetS. Jogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.
  PLoS ONE 01/2013; 8(1):e53258. · 4.09 Impact Factor
• Article: Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.

  Jing Dong, Guangfu Jin, Chen Wu, Huan Guo, Baosen Zhou, Jiachun Lv, Daru Lu, Yongyong Shi, Yongqian Shu, Lin Xu, [......], Ying Yan, Jibin Liu, Christopher I Amos, Feng Chen, Wen Tan, Li Jin, Tangchun Wu, Zhibin Hu, Dongxin Lin, Hongbing Shen
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  PLoS Genetics 01/2013; 9(1):e1003190. · 8.69 Impact Factor
• Article: [The dose response decrease of lung function associated with the urinary polycyclic aromatic hydrocarbons metabolites in coke oven workers].

  Die Hu, Qi-Fei Deng, Su-Li Huang, Yun-Feng He, Huan Guo, Tang-Chun Wu
  [show abstract] [hide abstract]
  ABSTRACT: To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage. We measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively. FEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all. The dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.
  Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 12/2012; 30(12):893-7.
• Source

  Available from: Keitaro Matsuo

  Article: Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

  Qing Lan, Chao A Hsiung, Keitaro Matsuo, Yun-Chul Hong, Adeline Seow, Zhaoming Wang, H Dean Hosgood, Kexin Chen, Jiu-Cun Wang, Nilanjan Chatterjee, [......], Hsien-Chih Lin, Tangchun Wu, Yi-Long Wu, Pan-Chyr Yang, Baosen Zhou, Min-Ho Shin, Joseph F Fraumeni, Dongxin Lin, Stephen J Chanock, Nathaniel Rothman
  [show abstract] [hide abstract]
  ABSTRACT: To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
  Nature Genetics 11/2012; · 35.53 Impact Factor
• Article: Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.

  Jing Dong, Zhibin Hu, Chen Wu, Huan Guo, Baosen Zhou, Jiachun Lv, Daru Lu, Kexin Chen, Yongyong Shi, Minjie Chu, [......], Yuxia Zhao, Haibo Zhang, Ying Yan, Christopher I Amos, Feng Chen, Wen Tan, Li Jin, Tangchun Wu, Dongxin Lin, Hongbing Shen
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  Nature Genetics 07/2012; 44(8):895-9. · 35.53 Impact Factor
• Article: Cohort profile: The Dongfeng-Tongji cohort study of retired workers.

  Feng Wang, Jiang Zhu, Ping Yao, Xiulou Li, Meian He, Yuewei Liu, Jing Yuan, Weihong Chen, Li Zhou, Xinwen Min, [......], Dongfeng Li, Chuanwen Lu, Xiaozheng Wang, Wenhu Shi, Jianru Zheng, Huan Guo, Xiaomin Zhang, Handong Yang, Frank B Hu, Tangchun Wu
  International Journal of Epidemiology 04/2012; · 6.41 Impact Factor
• Article: Genetic variations of CYP2B6 gene were associated with plasma BPDE-Alb adducts and DNA damage levels in coke oven workers.

  Guoxiang Huang, Huan Guo, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: Polycyclic aromatic hydrocarbons (PAHs), the main components of coke oven emissions, can induce activation of cytochrome P450 (CYP) enzymes, which metabolize PAHs and result in DNA damage by forming adducts. This study was designed to know whether genetic variants of CYP genes are associated with plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts and DNA damage in coke oven workers. In this study, 298 workers were divided into four groups according to the environmental PAHs exposure levels. The concentrations of plasma BPDE-Alb adducts were detected by reverse-phase high-performance liquid chromatography and the DNA damage levels were measured using comet assay. Twelve tag single nucleotide polymorphisms (tagSNPs) of 4 CYP genes were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the top group, workers with CYP2B6 rs3760657GA genotype have lower BPDE-Alb adducts and DNA damage levels than those with rs3760657GG genotype (P<0.05). In the control group, the DNA damage levels of subjects with CYP1A1 rs4646421AA or GA+AA genotypes were lower than those with GG genotype (P<0.05). However, no such effects were shown for the other tagSNPs. These results suggested that genetic variations of CYP2B6 might be associated with low BPDE-Alb adducts and DNA damage levels in worker with high exposure to PAHs.
  Toxicology Letters 04/2012; 211(3):232-8. · 3.23 Impact Factor
• Article: Clinical study on tongyan spray for post-stroke dysphagia patients: a randomized controlled trial.

  Xue-gong Feng, Wen-jie Hao, Zhou Ding, Qiang Sui, Huan Guo, Jian Fu
  [show abstract] [hide abstract]
  ABSTRACT: To observe the effectiveness and safety of Tongyan spray composed of Chinese medicine for post-stroke dysphagia patients. One hundred and twenty-two post-stroke dysphagia patients were randomly assigned to the treatment group (61 cases) and the control group (61 cases). Basic treatment was given to both groups, with Tongyan spray additionally used in oropharynx for the treatment group, and the placebo used for the control group. After 28-day treatment, the clinical effect and safety were evaluated according to the standard swallowing assessment (SSA) scale. One patient dropped out in each group, and 120 patients reached the final analysis of the study. The total effective rate for the treatment group was 71.7% (43/60), higher than 46.7% (28/60) in the control group (P<0.05), and the improvement on SSA scores of the two groups were significantly different after treatment (P<0.05). For grade 1 dysphagia patients (completely depending on nasogastric tube), the effective rate of the treatment group was 40.9% (9/22), and 12.5% (2/16) of the control group, without significant difference (P>0.05), while the improvement of SSA score was significantly different between the two groups after treatment (P<0.05). For grade 2-3 dysphagia patients (oral and nasogastric tube feeding), the total effective rate of the treatment group was 89.5% (34/38), higher than 59.1% (26/44) in the control group (P<0.05), and also the improvement on SSA scores was significantly different between the two groups after treatment (P<0.05). Tongyan spray was an effective and safe method for post-stroke dysphagia patients.
  Chinese Journal of Integrative Medicine 03/2012; 18(5):345-9. · 0.80 Impact Factor
• Article: Inlaid Nd-substituted bismuth titanate nanoplates for protein immobilization and Nd-controlled electrochemical properties.

  Huan Guo, Cui Ye, Hanchang He, Zhiwu Chen, Jianqiang Hu, Guanqi Hu, Aiqing Li
  [show abstract] [hide abstract]
  ABSTRACT: Neodymium (Nd) substituted bismuth titanate (Bi(4-x)Nd(x)Ti(3)O(12), BNTO-x) nanoplates inlaid one another were prepared by sol-gel hydrothermal method, which was explored for protein immobilization and biosensor fabrication. Comparative experiments witnessed that Bi(3+) ions in bismuth titanate (Bi(4)Ti(3)O(12), BTO) were successfully substituted with Nd(3+) ions, and the electrochemical properties of the Hb-Chi-BNTO biosensors closely depended on the Nd(3+) ion content. With increasing the Nd(3+) doping content, the electrochemical performance of the Hb-Chi-BNTO-x biosensors showed regularly variable. Moreover, compared with the Hb-Chi-BTO and other Hb-Chi-BNTO-x biosensors, the Hb-Chi-BNTO-0.85 biosensor had more excellent electrochemical and electrocatalytic properties such as stronger redox peak currents (approximately three-fold), smaller peak-to-peak separation (50 mV), larger heterogeneous electron transfer rate (14.1 ± 3.8s(-1)), higher surface concentration of electroactive redox protein (about 8.16 × 10(-11)mol/cm(2)), and better reproducibility and stability. The Nd-depended electrochemical properties of the Hb-Chi-BNTO biosensors may open up a new idea for designing third-generation electrochemical biosensors, and the BNTO-0.85-based biosensor is also expected to find potential applications in many areas such as biomedical, food, and environmental detection.
  Biosensors & bioelectronics 03/2012; 33(1):204-10. · 5.43 Impact Factor
• Article: Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant diabetes.

  Ming Liu, Roberto Lara-Lemus, Shu-ou Shan, Jordan Wright, Leena Haataja, Fabrizio Barbetti, Huan Guo, Dennis Larkin, Peter Arvan
  [show abstract] [hide abstract]
  ABSTRACT: Recently, missense mutations upstream of preproinsulin's signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER-oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY.
  Diabetes 02/2012; 61(4):828-37. · 8.29 Impact Factor
• Article: Effects of petroleum contamination on soil microbial numbers, metabolic activity and urease activity.

  Huan Guo, Jun Yao, Minmin Cai, Yiguang Qian, Yue Guo, Hans H Richnow, Ruth E Blake, Serena Doni, Brunello Ceccanti
  [show abstract] [hide abstract]
  ABSTRACT: The influence of petroleum contamination on soil microbial activities was investigated in 13 soil samples from sites around an injection water well (Iw-1, 2, 3, 4) (total petroleum hydrocarbons (TPH): 7.5-78 mg kg(-1)), an oil production well (Op-1, 2, 3, 4, 5) (TPH: 149-1110 mg kg(-1)), and an oil spill accident well (Os-1, 2, 3, 4) (TPH: 4500-34600 mg kg(-1)). The growth rate constant (μ) of glucose stimulated organisms, determined by microcalorimetry, was higher in Iw soil samples than in Op and Os samples. Total cultivable bacteria and fungi and urease activity also decreased with increasing concentration of TPH. Total heat produced demonstrated that TPH at concentrations less than about 1 g kg(-1) soil stimulated anaerobic respiration. A positive correlation between TPH and soil organic matter (OM) and stimulation of fungi-bacteria-urease at low TPH doses suggested that TPH is bound to soil OM and slowly metabolized in Iw soils during OM consumption. These methods can be used to evaluate the potential of polluted soils to carry out self-bioremediation by metabolizing TPH.
  Chemosphere 02/2012; 87(11):1273-80. · 3.21 Impact Factor
• Article: The dose-response decrease in heart rate variability: any association with the metabolites of polycyclic aromatic hydrocarbons in coke oven workers?

  Xiaohai Li, Yingying Feng, Huaxin Deng, Wangzhen Zhang, Dan Kuang, Qifei Deng, Xiayun Dai, Dafeng Lin, Suli Huang, Lili Xin, Yunfeng He, Kun Huang, Meian He, Huan Guo, Xiaomin Zhang, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: Air pollution has been associated with an increased risk of cardiopulmonary mortality and decreased heart rate variability (HRV). However, it is unclear whether coke oven emissions (COEs) and polycyclic aromatic hydrocarbons (PAHs) are associated with HRV. Our goal in the present study was to investigate the association of exposure to COEs and the urinary metabolite profiles of PAHs with HRV of coke oven workers. We measured benzene soluble matter, carbon monoxide, sulfur dioxide, particulate matters, and PAHs at different workplaces of a coke oven plant. We determined 10 urinary PAH metabolites and HRV indices of 1333 workers using gas chromatography-mass spectrometry and a 3-channel digital Holter monitor, respectively. Our results showed that there was a significant COEs-related dose-dependent decrease in HRV, and an inverse relationship between the quartiles of urinary 2-hydroxynaphthalene and five HRV indices (p(trend)<0.01 for all). After adjustment for potential confounders, elevation per interquartile range (IQR) (1.81 µg/mmol creatinine) of urinary 2-hydroxynaphthalene was associated with a 5.46% (95% CI, 2.50-8.32) decrease in standard deviation of NN intervals (SDNN). As workers worked more years, SDNN gradually declined in the same quartiles of 2-hydroxynaphthalene levels (p(trend) = 1.40×10(-4)), especially in workers with the highest levels of 2-hydroxynaphthalene. Occupational exposure to COEs is associated with a dose-response decrease in HRV. In particular, increased exposure to 2-hydroxynaphthalene is associated with significantly decreased HRV. Increase of working years and exposure levels has resulted in a gradual decline of HRV.
  PLoS ONE 01/2012; 7(9):e44562. · 4.09 Impact Factor
• Article: Variations in HSPA1B at 6p21.3 are associated with lung cancer risk and prognosis in Chinese populations.

  Huan Guo, Qifei Deng, Chen Wu, Lingmin Hu, Sheng Wei, Ping Xu, Dan Kuang, Li Liu, Zhibin Hu, Xiaoping Miao, Hongbing Shen, Dongxin Lin, Tangchun Wu
  [show abstract] [hide abstract]
  ABSTRACT: The heat shock protein Hsp70 is crucial for regulating cellular homeostasis in stressed cells. Although the tumorigenic potential and prognostic applications of Hsp70 have been widely investigated, it remains unclear whether genetic variations of the human isoforms HSPA1L, HSPA1A, and HSPA1B are associated with cancer risk and prognosis. In this study, we genotyped six tagSNPs in these genes in 1,152 paired patients with lung cancer and controls, and then validated the results in additional cohorts of 1,781 patients with lung cancer and 1,038 controls. In addition, we evaluated the associations of these tagSNPs with survival in 330 patients with advanced non-small cell lung cancer (NSCLC) with additional validation in another 331 patients with advanced NSCLC. Functions of the risk variants identified were investigated using cell-based reporter assays. We found that the HSPA1B rs6457452T allele was associated with increased lung cancer risk compared with the rs6457452C allele in both data sets and also pooled analysis (adjusted OR = 1.41; P = 2.8 × 10(-5)). The HSPA1B rs2763979TT genotype conferred poor survival outcomes for patients with advanced NSCLC in two independent cohorts and pooled analysis [adjusted hazard ratio (HR) = 1.80, 1.61, and 1.66; P = 0.013, 0.036, and 0.002, respectively]. Lastly, we also found that the rs2763979T and rs6457452T alleles were each sufficient to reduce expression of transcriptional reporter constructs, when compared with the rs2763979C and rs6457452C alleles, respectively. Taken together, our findings define that functional HSPA1B variants are associated with lung cancer risk and survival. These Hsp70 genetic variants may offer useful biomarkers to predict lung cancer risk and prognosis.
  Cancer Research 12/2011; 71(24):7576-86. · 7.86 Impact Factor
• Article: [Relevance between single nucleotide polymorphisms in nicotinic acetylcholine receptor genes and DNA damage levels in coke oven workers].

  Yi-xiao Tu, Huan Guo, Tang-chun Wu
  [show abstract] [hide abstract]
  ABSTRACT: To investigate the relevance between single nucleotide polymorphisms (SNPs) in CHRNA3-CHRNB4-CHRNA5 gene cluster and DNA damage levels in the coke oven workers. A total of 309 male subjects from a steel plant in Northern China were divided into high exposure group (154 workers) and low exposure group (155 workers) according to the concentrations of plasma benzoapyrene-r-7, t-8, t-9, c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts. DNA damage levels of peripheral blood lymphocytes were examined by comet assay. Allelic discrimination of SNPs in CHRNA3-CHRNB4-CHRNA5 gene cluster were detected using Matrix-assisted laser desorption/ionization mass spectrometry. The Olive tail moment (OTM) (1.23 ± 1.05) of peripheral blood lymphocytes in the high exposure group was significantly higher than that (0.80 ± 1.07) in the low exposure group (P < 0.01). In the high exposure group, OTM (1.64 ± 0.17) of subjects with rs667282CC genotype was significantly higher than those (0.95 ± 0.13 or 1.09 ± 0.11) of subjects with rs667282CT genotype or rs667282TT + CT genotype (P < 0.01); OTM (1.60 ± 0.17) of subjects with GG genotype at rs12910984 site was significantly higher than those (0.92 ± 0.13 or 1.07 ± 0.10) of subjects with AG genotype or AG + AA genotype (P < 0.01); OTM (1.35 ± 0.17 or 1.64 ± 0.17) of the TA/TA or CG/CG diplotype carriers was significantly higher than that (0.89 ± 0.13) of TA/CG diplotype carriers (P < 0.05). However, the relevance between genotypes of these SNPs and the DNA damage levels was not found in the low exposure group. The rs667282CC genotype and rs12910984GG genotype on CHRNA3-CHRNB4-CHRNA5 gene cluster are associated with increased DNA damage levels in the high PAHs exposure group.
  Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 10/2011; 29(10):726-30.
• Source

  Available from: Jiachun Lu

  Article: A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.

  Zhibin Hu, Chen Wu, Yongyong Shi, Huan Guo, Xueying Zhao, Zhihua Yin, Lei Yang, Juncheng Dai, Lingmin Hu, Wen Tan, [......], Zhengdong Zhang, Feng Chen, Xinru Wang, Li Jin, Jiachun Lu, Baosen Zhou, Daru Lu, Tangchun Wu, Dongxin Lin, Hongbing Shen
  [show abstract] [hide abstract]
  ABSTRACT: Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.
  Nature Genetics 07/2011; 43(8):792-6. · 35.53 Impact Factor
• Article: A functional -77T>C polymorphism in XRCC1 is associated with risk of breast cancer.

  Li Liu, Peng Yuan, Chen Wu, Xiaomin Zhang, Huan Guo, Rong Zhong, Yihua Xu, Jing Wu, Shengyu Duan, Rui Rui, Tangchun Wu, Shaofa Nie, Xiaoping Miao, Dongxin Lin
  [show abstract] [hide abstract]
  ABSTRACT: X-ray repair cross-complementing 1 (XRCC1) plays a critical role in base excision repair and genetic variations of XRCC1 may be associated with cancer susceptibility. We tested this hypothesis by examining the contribution of polymorphism in the regulatory region of XRCC1 -77T>C to risk of breast cancer in 995 patients and 1,004 controls. We found this polymorphism was associated with an increased risk of breast cancer, with an OR of 1.25 (95% CI, 1.00-1.56) for the -77TC genotype and 2.55 (95% CI, 1.11-5.86) for the -77CC genotype compared with the -77TT genotype. Haplotype analysis combining the -77T>C with three well-studied non-synonymous polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) showed that only the -77C-containing haplotype was associated with the risk. Moreover, the C allele had more than 3-fold decreased luciferase expression compared with the T allele in breast cancer cell line MCF-7 (P < 0.001). A meta-analysis of seven publications with a total 2,888 cancer cases and 3,177 controls demonstrated that -77C was significantly associated with cancer risk, with an OR of 1.34 (95% CI, 1.18-1.51) for the TC genotype and 1.53 (95% CI, 1.14-2.07) for the CC genotype compared with the TT genotype. In conclusion, these findings indicated that XRCC1 -77T>C polymorphism may be a genetic determinant for developing breast cancer.
  Breast Cancer Research and Treatment 01/2011; 125(2):479-87. · 4.43 Impact Factor
• Article: Increased levels of lead in the blood and frequencies of lymphocytic micronucleated binucleated cells among workers from an electronic-waste recycling site.

  Qian Wang, An M He, Bo Gao, Lan Chen, Qiang Z Yu, Huan Guo, Bin J Shi, Pu Jiang, Zeng Y Zhang, Ping L Li, Ying G Sheng, Mo J Fu, Chun T Wu, Min X Chen, Jing Yuan
  [show abstract] [hide abstract]
  ABSTRACT: In recent years, adverse health effects of chemicals from electronic waste (e-waste) have been reported. However, little is known about the genotoxic effects of chemicals in e-waste. In the present study, air concentrations of the toxic metals at e-waste and control sites were analyzed using inductively-coupled plasma mass spectrometry. Levels of toxic metals (lead, copper and cadmium) in blood and urine were detected using atomic absorption spectrophotometry in 48 exposed individuals and 56 age- and sex-matched controls. The frequencies of lymphocytic micronucleated binucleated cells (MNBNCs) were determined using a cytokinesis-block micronucleus assay. Results indicated that blood lead levels were significantly higher in the exposed group (median: 11.449 μg/dL, 1st/3rd quartiles: 9.351-14.410 μg/dL) than in the control group (median: 9.104 μg/dL, 1st/3rd quartiles: 7.275-11.389 μg/dL). The exposed group had higher MNBNCs frequencies (median: 4.0 per thousand, 1st/3rd quartiles: 2.0-7.0 per thousand) compared with the controls (median: 1.0 per thousand, 1st/3rd quartiles: 0.0-2.0 per thousand). Additionally, MNBNCs frequencies and blood lead levels were positively correlated (r = 0.254, p<0.01). Further analysis suggested that a history of working with e-waste was a predictor for increased blood lead levels and MNBNCs frequencies in the subjects. The results suggest that both the living and occupational environments at the e-waste site may be risk factors for increased MNBNCs frequencies among those who are exposed.
  Journal of Environmental Science and Health Part A Toxic/Hazardous Substances & Environmental Engineering 01/2011; 46(6):669-76.