65 results on '"Hongbing, Shen"'
Search Results
2. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.
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Robert Carreras-Torres, Mattias Johansson, Philip C Haycock, Kaitlin H Wade, Caroline L Relton, Richard M Martin, George Davey Smith, Demetrius Albanes, Melinda C Aldrich, Angeline Andrew, Susanne M Arnold, Heike Bickeböller, Stig E Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E Caporaso, Chu Chen, David C Christiani, W Jay Christian, Jennifer A Doherty, Eric J Duell, John K Field, Michael P A Davies, Michael W Marcus, Gary E Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A Kiemeney, Erik H F M van der Heijden, Peter Kraft, Mikael B Johansson, Stephen Lam, Maria Teresa Landi, Philip Lazarus, Loïc Le Marchand, Geoffrey Liu, Olle Melander, Sungshim L Park, Gad Rennert, Angela Risch, Eric B Haura, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milan Savić, Jolanta Lissowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Dana Mates, Matthew B Schabath, Hongbing Shen, Adonina Tardon, M Dawn Teare, Penella Woll, Ming-Sound Tsao, Xifeng Wu, Jian-Min Yuan, Rayjean J Hung, Christopher I Amos, James McKay, and Paul Brennan more...
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Medicine ,Science - Abstract
BACKGROUND:Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS:We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS:Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior. more...
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- 2017
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3. Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.
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Liyan Jiang, Jiaqi Huang, Brandon W Higgs, Zhibin Hu, Zhan Xiao, Xin Yao, Sarah Conley, Haihong Zhong, Zheng Liu, Philip Brohawn, Dong Shen, Song Wu, Xiaoxiao Ge, Yue Jiang, Yizhuo Zhao, Yuqing Lou, Chris Morehouse, Wei Zhu, Yinong Sebastian, Meggan Czapiga, Vaheh Oganesyan, Haihua Fu, Yanjie Niu, Wei Zhang, Katie Streicher, David Tice, Heng Zhao, Meng Zhu, Lin Xu, Ronald Herbst, Xinying Su, Yi Gu, Shyoung Li, Lihua Huang, Jianren Gu, Baohui Han, Bahija Jallal, Hongbing Shen, and Yihong Yao more...
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Genetics ,QH426-470 - Abstract
Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC. more...
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- 2016
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4. A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.
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Ye Sun, Cheng Wang, Zheng Hao, Jin Dai, Dongyang Chen, Zhihong Xu, Dongquan Shi, Ping Mao, Huajian Teng, Xiang Gao, Zhibin Hu, Hongbing Shen, and Qing Jiang
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Medicine ,Science - Abstract
Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH.We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A.Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population. more...
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- 2015
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5. Low Goiter Rate Associated with Small Average Thyroid Volume in Schoolchildren after the Elimination of Iodine Deficiency Disorders.
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Peihua Wang, Hong Sun, Li Shang, Qinglan Zhang, Yingxia He, Zhigao Chen, Yonglin Zhou, Jingjing Zhang, Qingqing Wang, Jinkou Zhao, and Hongbing Shen
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Medicine ,Science - Abstract
After the implementation of the universal salt iodization (USI) program in 1996, seven cross-sectional school-based surveys have been conducted to monitor iodine deficiency disorders (IDD) among children in eastern China.This study aimed to examine the correlation of total goiter rate (TGR) with average thyroid volume (Tvol) and urinary iodine concentration (UIC) in Jiangsu province after IDD elimination.Probability-proportional-to-size sampling was applied to select 1,200 children aged 8-10 years old in 30 clusters for each survey in 1995, 1997, 1999, 2001, 2002, 2005, 2009 and 2011. We measured Tvol using ultrasonography in 8,314 children and measured UIC (4,767 subjects) and salt iodine (10,184 samples) using methods recommended by the World Health Organization. Tvol was used to calculate TGR based on the reference criteria specified for sex and body surface area (BSA).TGR decreased from 55.2% in 1997 to 1.0% in 2009, and geometric means of Tvol decreased from 3.63 mL to 1.33 mL, along with the UIC increasing from 83 μg/L in 1995 to 407 μg/L in 1999, then decreasing to 243 μg/L in 2005, and then increasing to 345 μg/L in 2011. In the low goiter population (TGR < 3.9%), TGR was positively associated with average Tvol (r = 0.99); UIC showed a non-linear association with average Tvol, and UIC > 300 μg/L was associated with a smaller average Tvol in children.After IDD elimination in Jiangsu province in 2001, lower TGR was associated with smaller average Tvol. Average Tvol was more sensitive than TGR in detecting the fluctuation of UIC. A UIC of 300 μg/L may be defined as a critical value for population level iodine status monitoring. more...
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- 2015
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6. Cumulative effect and predictive value of genetic variants associated with type 2 diabetes in Han Chinese: a case-control study.
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Yun Qian, Feng Lu, Meihua Dong, Yudi Lin, Huizhang Li, Juncheng Dai, Guangfu Jin, Zhibin Hu, and Hongbing Shen
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Medicine ,Science - Abstract
Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We have previously confirmed the associations of genetic variants in HHEX, CDKAL1, VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes in Han Chinese are largely unknown.We conducted a two-stage case-control study consisting of 2,925 cases and 3,281 controls to examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio (OR) = 1.41, P = 9.91 × 10-16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34 × 10-10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 × 10-4 for rs1552224) and SLC30A8 (OR = 1.19, P = 1.43 × 10-5 for rs13266634). We further evaluated the cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or more risk alleles had a nearly 4-fold increased risk for developing type 2 diabetes compared with those carrying less than 6 risk alleles [adjusted OR = 3.68, 95% confidence interval (CI): 2.76-4.91]. Adding the genetic factors to clinical factors slightly improved the prediction of type 2 diabetes, with the area under the receiver operating characteristic curve increasing from 0.76 to 0.78. However, the difference was statistically significant (P < 0.0001).We confirmed associations of SNPs in KCNQ1, CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The utilization of genetic information may improve the accuracy of risk prediction in combination with clinical characteristics for type 2 diabetes. more...
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- 2015
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7. Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers--Hepatocellular Carcinoma and Cervical Cancer.
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Jian Yin, Juan Wen, Dong Hang, Jing Han, Jie Jiang, Ci Song, Yao Liu, Jibin Liu, Li Liu, Liguo Zhu, Jianguo Chen, Xiangjun Zhai, Shuanghua Xie, Zhibin Hu, Hongbing Shen, Min Dai, and Ni Li
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Medicine ,Science - Abstract
Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03-1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09-1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer. more...
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- 2015
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8. Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population.
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Ping Sun, Jiangbo Du, Xun Zhu, Chuanli Ren, Lan Xie, Ningbin Dai, Yayun Gu, Caiwang Yan, Juncheng Dai, Hongxia Ma, Yue Jiang, Jiaping Chen, Zhibin Hu, Hongbing Shen, Haorong Wu, and Guangfu Jin
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Medicine ,Science - Abstract
NBN plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the NBN gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the NBN gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in NBN and gastric cancer risk in a case-control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71-0.94; P = 4.71×10-3). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59-0.88], P = 1.07×10-3), and male individuals (per-allele OR = 0.73[0.62-0.87], P = 3.68×10-4). We further conducted a haplotype analysis and identified that the NBN Ars10464867Grs14448Grs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65-0.89], P = 6.39×10-4). In summary, these findings indicate that genetic variants at NBN gene may contribute to gastric cancer susceptibility and may further advance our understanding of NBN gene in cancer development. more...
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- 2015
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9. Circulating Tumor Cells Enriched by the Depletion of Leukocytes with Bi-Antibodies in Non-Small Cell Lung Cancer: Potential Clinical Application.
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Jian Yin, Yi Wang, Hanlu Yin, Wenping Chen, Guangfu Jin, Hongxia Ma, Juncheng Dai, Jiaping Chen, Yue Jiang, Hui Wang, Zhian Liu, Zhibin Hu, and Hongbing Shen
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Medicine ,Science - Abstract
It has been considered that the detection methods for circulating tumor cells (CTCs) based on epithelial cell adhesion molecule (EpCAM) underestimate the number of CTCs and may miss a metastatic subpopulation with cancer stem cell (CSC) properties. Therefore, we investigated EpCAM-positive and -negative CTCs in non-small cell lung cancer (NSCLC) patients at different stages, assessed the clinical value of these CTCs and explored their capacity in the following CSC model.CTCs were enriched by the depletion of leukocytes with bi-antibodies using a magnetic bead separation technique and then identified by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow cytometry. We determined the distribution of CTCs classified by the expression of EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy and characterized the stemness of these CTCs by the expression of CXCR4 and CD133 in 10 patients.EpCAM-negative (E-) CTCs were detected to be significantly higher than EpCAM-positive (E+) CTCs in stage IV (p = 0.003). The patients with the percentage of E-CTCs more than 95% (r > 95%) were detected to be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p = 0.006). Kaplan-Meier analysis indicated that the patients with r > 95% had significantly shorter survival time than those with r ≤ 0.95 (p = 0.041). Longitudinal monitoring of CTCs indicated that the patients with a high percentage of E-CTCs in the blood were not responsive to either chemotherapy or targeted therapy. Further characterization of CTCs revealed that a stem-like subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more prevalent in E-CTCs than that in E+CTCs (p = 0.005).The enrichment of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method for estimating the number of CTCs, which can be potentially applied in predicting the prognosis, monitoring the therapeutic effect of NSCLC patients and further analyzing the biology of CTCs. more...
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- 2015
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10. Spatio-temporal trends and risk factors for Shigella from 2001 to 2011 in Jiangsu Province, People's Republic of China.
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Fenyang Tang, Yuejia Cheng, Changjun Bao, Jianli Hu, Wendong Liu, Qi Liang, Ying Wu, Jessie Norris, Zhihang Peng, Rongbin Yu, Hongbing Shen, and Feng Chen
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Medicine ,Science - Abstract
ObjectiveThis study aimed to describe the spatial and temporal trends of Shigella incidence rates in Jiangsu Province, People's Republic of China. It also intended to explore complex risk modes facilitating Shigella transmission.MethodsCounty-level incidence rates were obtained for analysis using geographic information system (GIS) tools. Trend surface and incidence maps were established to describe geographic distributions. Spatio-temporal cluster analysis and autocorrelation analysis were used for detecting clusters. Based on the number of monthly Shigella cases, an autoregressive integrated moving average (ARIMA) model successfully established a time series model. A spatial correlation analysis and a case-control study were conducted to identify risk factors contributing to Shigella transmissions.ResultsThe far southwestern and northwestern areas of Jiangsu were the most infected. A cluster was detected in southwestern Jiangsu (LLR = 11674.74, PConclusionImprovement of sanitation and hygiene should be strengthened in economically developed counties, while access to a safe water supply in impoverished areas should be increased at the same time. more...
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- 2014
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11. Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.
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Dong Li, Lixuan Wei, Binghe Xu, Dianke Yu, Jiang Chang, Peng Yuan, Zhongli Du, Wen Tan, Hongbing Shen, Tangchun Wu, Chen Wu, and Dongxin Lin
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Medicine ,Science - Abstract
Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs) identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC). Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A), 22q12.2 (rs36600C >T) and 5p15.33 (rs401681C >T), significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR) for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187) and 0.73 (95% CI, 0.55-0.96; P = 0.0263) compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199) and 1.29 (95% CI, 1.08-1.55; P = 0.0047), respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC. more...
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- 2014
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12. Evaluation of the impact of hepatitis B vaccination in adults in Jiangsu province, China.
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Liguo Zhu, Xiangjun Zhai, Yefei Zhu, Weiguo Xu, Changjun Bao, Hong Peng, Qian Bian, Haitao Yang, Hua Wang, Zhibin Hu, and Hongbing Shen
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Medicine ,Science - Abstract
Hepatitis B immunization programs for newborns, children, and adolescents in China have shown remarkable results. To establish whether there would be any benefit in extending the program to cover older individuals, we examined both the epidemiology of hepatitis B virus (HBV) infection and the coverage of hepatitis B vaccinations among adults born before routine vaccinations were implemented. We then evaluated the impact of hepatitis B vaccination in adults aged 20-59 years. A large-scale cross-sectional epidemiological survey of HBV infection was performed in the province of Jiangsu, south-east China, between September 2009 and March 2010. A total of 86,732 adults aged 20-59 years were included, of which 8,615 (9.9%, 95% CI = 9.7-10.1%) were HBsAg sero-positive. Self-reported vaccination status suggested that the coverage was approximately 23.7% (95% CI = 23.4-24.0%). It was shown that higher HBV vaccination coverage was associated with a lower rate of HBsAg seropositivity among adults. There was a negative correlation between hepatitis B vaccination coverage and HBsAg prevalence (correlation coefficient = -0.805, p = 0.016), which might demonstrate the combined effects of vaccination and pre-vaccination HBsAg screening. In the unvaccinated group, the HBsAg-positive rate had an obvious upward trend with age growing among 20-39 year-olds (Trend χ2 = 22.605, P more...
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- 2014
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13. Replication of the 4p16 susceptibility locus in congenital heart disease in Han Chinese populations.
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Bijun Zhao, Yuan Lin, Jing Xu, Bixian Ni, Min Da, Chenyue Ding, Yuanli Hu, Kai Zhang, Shiwei Yang, Xiaowei Wang, Shiqiang Yu, Yijiang Chen, Xuming Mo, Jiayin Liu, Hongbing Shen, Jiahao Sha, and Hongxia Ma more...
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Medicine ,Science - Abstract
Congenital heart disease (CHD) is the most common form of congenital human birth anomalies and a leading cause of perinatal and infant mortality. Some studies including our published genome-wide association study (GWAS) of CHD have indicated that genetic variants may contribute to the risk of CHD. Recently, Cordell et al. published a GWAS of multiple CHD phenotypes in European Caucasians and identified 3 susceptibility loci (rs870142, rs16835979 and rs6824295) for ostium secundum atrial septal defect (ASD) at chromosome 4p16. However, whether these loci at 4p16 confer the predisposition to CHD in Chinese population is unclear. In the current study, we first analyzed the associations between these 3 single nucleotide polymorphisms (SNPs) at 4p16 and CHD risk by using our existing genome-wide scan data and found all of the 3 SNPs showed significant associations with ASD in the same direction as that observed in Cordell's study, but not with other subtypes- ventricular septal defect (VSD) and ASD combined VSD. As these 3 SNPs were in high linkage disequilibrium (LD) in Chinese population, we selected one SNP with the lowest P value in our GWAS scan (rs16835979) to perform a replication study with additional 1,709 CHD cases with multiple phenotypes and 1,962 controls. The significant association was also observed only within the ASD subgroup, which was heterogeneous from other disease groups. In combined GWAS and replication samples, the minor allele of rs16835979 remained significant association with the risk of ASD (OR = 1.22, 95% CI = 1.08-1.38, P = 0.001). Our findings suggest that susceptibility loci of ASD identified from Cordell's European GWAS are generalizable to Chinese population, and such investigation may provide new insights into the roles of genetic variants in the etiology of different CHD phenotypes. more...
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- 2014
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14. The spatial analysis on hemorrhagic fever with renal syndrome in Jiangsu province, China based on geographic information system.
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Changjun Bao, Wanwan Liu, Yefei Zhu, Wendong Liu, Jianli Hu, Qi Liang, Yuejia Cheng, Ying Wu, Rongbin Yu, Minghao Zhou, Hongbing Shen, Feng Chen, Fenyang Tang, and Zhihang Peng
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Medicine ,Science - Abstract
Hemorrhagic fever with renal syndrome (HFRS) is endemic in mainland China, accounting for 90% of total reported cases worldwide, and Jiangsu is one of the most severely affected provinces. In this study, the authors conducted GIS-based spatial analyses in order to determine the spatial distribution of the HFRS cases, identify key areas and explore risk factors for public health planning and resource allocation.Interpolation maps by inverse distance weighting were produced to detect the spatial distribution of HFRS cases in Jiangsu from 2001 to 2011. Spatio-temporal clustering was applied to identify clusters at the county level. Spatial correlation analysis was conducted to detect influencing factors of HFRS in Jiangsu.HFRS cases in Jiangsu from 2001 to 2011 were mapped and the results suggested that cases in Jiangsu were not distributed randomly. Cases were mainly distributed in northeastern and southwestern Jiangsu, especially in Dafeng and Sihong counties. It was notable that prior to this study, Sihong county had rarely been reported as a high-risk area of HFRS. With the maximum spatial size of 50% of the total population and the maximum temporal size of 50% of the total population, spatio-temporal clustering showed that there was one most likely cluster (LLR = 624.52, P more...
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- 2014
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15. A genetic variant in the promoter region of miR-106b-25 cluster predict clinical outcome of HBV-related hepatocellular carcinoma in Chinese.
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Fuzhen Qi, Mingde Huang, Yun Pan, Yao Liu, Jibin Liu, Juan Wen, Kaipeng Xie, Hongbing Shen, Hongxia Ma, Yi Miao, and Zhibin Hu
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Medicine ,Science - Abstract
BACKGROUND: MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients. METHODS: The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis. RESULTS: The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) = 0.76,95% confidence intervals (CI) = 0.59-0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR = 0.72, 95% CI = 0.56-0.91, P = 0.007). CONCLUSIONS: These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese. more...
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- 2014
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16. Genetic variants at 10p11 confer risk of Tetralogy of Fallot in Chinese of Nanjing.
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Jing Xu, Yuan Lin, Linjie Si, Guangfu Jin, Juncheng Dai, Cheng Wang, Jiaping Chen, Min Da, Yuanli Hu, Chenlong Yi, Zhibin Hu, Hongbing Shen, Xuming Mo, Yijiang Chen, and Xiaowei Wang
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Medicine ,Science - Abstract
A recent genome-wide association study (GWAS) has identified a new subset of susceptibility loci of Tetralogy of Fallot (TOF), one form of cyanotic congenital heart disease (CHD), on chromosomes 10p11, 10p14, 12q24, 13q31, 15q13 and 16q12 in Europeans. In the current study, we conducted a case-control study in a Chinese population including 1,010 CHD cases [atrial septal defect (ASD), ventricular septal defect (VSD) and TOF] and 1,962 controls to evaluate the associations of these loci with risk of CHD. We found that rs2228638 in NRP1 on 10p11 was significantly increased the risk of TOF (OR = 1.52, 95% CI = 1.13-2.04, P = 0.006), but not in other subgroups including ASD and VSD. In addition, no significant associations were observed between the other loci and the risk of ASD, VSD or TOF. Our results suggested that the genetic variants on 10p11 may serve as candidate markers for TOF susceptibility in Chinese population. more...
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- 2014
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17. Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer.
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Jiaping Chen, Zhenzhen Qin, Yue Jiang, Yanru Wang, Yisha He, Juncheng Dai, Guangfu Jin, Hongxia Ma, Zhibin Hu, Yongmei Yin, and Hongbing Shen
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Medicine ,Science - Abstract
Genetic variants in human microRNA (miRNA) genes may alter mature miRNA processing and/or target selection, and likely contribute to cancer susceptibility and disease progression. Previous studies have suggested that miR-101 may play important roles in the development of cancer by regulating key tumor-associated genes. However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in breast cancer susceptibility remains unclear. In this study, we genotyped 11 SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study of 1064 breast cancer cases and 1073 cancer-free controls. The results revealed that rs462480 and rs1053872 in the flank regions of pre-miR-101-2 were significantly associated with increased risk of breast cancer (rs462480 AC/CC vs AA: adjusted OR = 1.182, 95% CI: 1.030-1.357, P = 0.017; rs1053872 CG/GG vs CC: adjusted OR = 1.179, 95% CI: 1.040-1.337, P = 0.010). However, the remaining 9 SNPs were not significantly associated with risk of breast cancer. Additionally, combined analysis of the two high-risk SNPs revealed that subjects carrying the variant genotypes of rs462480 and rs1053872 had increased risk of breast cancer in a dose-response manner (P(trend) = 0.002). Compared with individuals with "0-1" risk allele, those carrying "2-4" risk alleles had 1.29-fold risk of breast cancer. In conclusion, these findings suggested that the SNPs rs462480 and rs1053872 residing in miR-101-2 gene may have a solid impact on genetic susceptibility to breast cancer, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis. more...
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- 2014
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18. A genetic variant in primary miR-378 is associated with risk and prognosis of hepatocellular carcinoma in a Chinese population.
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Jiaze An, Jibin Liu, Li Liu, Yao Liu, Yun Pan, Mingde Huang, Fuzhen Qi, Juan Wen, Kaipeng Xie, Hongxia Ma, Hongbing Shen, and Zhibin Hu
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Medicine ,Science - Abstract
BACKGROUND: MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis. METHODS: We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment. RESULTS: The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81-1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59-0.83, P more...
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- 2014
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19. Population aging and migrant workers: bottlenecks in tuberculosis control in rural China.
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Sumedh Bele, Wei Jiang, Hui Lu, Hua You, Hong Fan, Lifang Huang, Qungang Wang, Hongbing Shen, and Jianming Wang
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Medicine ,Science - Abstract
BACKGROUND: Tuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China. METHODS: A qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software. RESULTS: Health providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients. CONCLUSION: The results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level. more...
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- 2014
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20. Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.
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Miaofei Xu, Yufeng Qin, Jianhua Qu, Chuncheng Lu, Ying Wang, Wei Wu, Ling Song, Shoulin Wang, Feng Chen, Hongbing Shen, Jiahao Sha, Zhibin Hu, Yankai Xia, and Xinru Wang
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA). OBJECTIVE: To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia. DESIGN SETTING AND PARTICIPANTS: A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011. MEASUREMENTS: We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping. RESULTS AND LIMITATIONS: Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P = 0.005, 95%CI 1.58-13.4) and 1.82 (P = 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings. CONCLUSIONS: Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future. more...
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- 2013
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21. Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.
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Jing Dong, Guangfu Jin, Chen Wu, Huan Guo, Baosen Zhou, Jiachun Lv, Daru Lu, Yongyong Shi, Yongqian Shu, Lin Xu, Minjie Chu, Cheng Wang, Ruyang Zhang, Juncheng Dai, Yue Jiang, Dianke Yu, Hongxia Ma, Xueying Zhao, Zhihua Yin, Lei Yang, Zhiqiang Li, Qifei Deng, Songyu Cao, Zhenzhen Qin, Jianhang Gong, Chongqi Sun, Jiucun Wang, Wei Wu, Guoquan Zhou, Hongyan Chen, Peng Guan, Yijiang Chen, Xiangyang Liu, Li Liu, Pin Xu, Baohui Han, Chunxue Bai, Yuxia Zhao, Haibo Zhang, Ying Yan, Jibin Liu, Christopher I Amos, Feng Chen, Wen Tan, Li Jin, Tangchun Wu, Zhibin Hu, Dongxin Lin, and Hongbing Shen more...
- Subjects
Genetics ,QH426-470 - 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. more...
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- 2013
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22. Pathway analysis for genome-wide association study of lung cancer in Han Chinese population.
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Ruyang Zhang, Yang Zhao, Minjie Chu, Chen Wu, Guangfu Jin, Juncheng Dai, Cheng Wang, Lingmin Hu, Jianwei Gou, Chen Qian, Jianling Bai, Tangchun Wu, Zhibin Hu, Dongxin Lin, Hongbing Shen, and Feng Chen more...
- Subjects
Medicine ,Science - Abstract
Genome-wide association studies (GWAS) have identified a number of genetic variants associated with lung cancer risk. However, these loci explain only a small fraction of lung cancer hereditability and other variants with weak effect may be lost in the GWAS approach due to the stringent significance level after multiple comparison correction. In this study, in order to identify important pathways involving the lung carcinogenesis, we performed a two-stage pathway analysis in GWAS of lung cancer in Han Chinese using gene set enrichment analysis (GSEA) method. Predefined pathways by BioCarta and KEGG databases were systematically evaluated on Nanjing study (Discovery stage: 1,473 cases and 1,962 controls) and the suggestive pathways were further to be validated in Beijing study (Replication stage: 858 cases and 1,115 controls). We found that four pathways (achPathway, metPathway, At1rPathway and rac1Pathway) were consistently significant in both studies and the P values for combined dataset were 0.012, 0.010, 0.022 and 0.005 respectively. These results were stable after sensitivity analysis based on gene definition and gene overlaps between pathways. These findings may provide new insights into the etiology of lung cancer. more...
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- 2013
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23. Weighted SNP set analysis in genome-wide association study.
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Hui Dai, Yang Zhao, Cheng Qian, Min Cai, Ruyang Zhang, Minjie Chu, Juncheng Dai, Zhibin Hu, Hongbing Shen, and Feng Chen
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Medicine ,Science - Abstract
Genome-wide association studies (GWAS) are popular for identifying genetic variants which are associated with disease risk. Many approaches have been proposed to test multiple single nucleotide polymorphisms (SNPs) in a region simultaneously which considering disadvantages of methods in single locus association analysis. Kernel machine based SNP set analysis is more powerful than single locus analysis, which borrows information from SNPs correlated with causal or tag SNPs. Four types of kernel machine functions and principal component based approach (PCA) were also compared. However, given the loss of power caused by low minor allele frequencies (MAF), we conducted an extension work on PCA and used a new method called weighted PCA (wPCA). Comparative analysis was performed for weighted principal component analysis (wPCA), logistic kernel machine based test (LKM) and principal component analysis (PCA) based on SNP set in the case of different minor allele frequencies (MAF) and linkage disequilibrium (LD) structures. We also applied the three methods to analyze two SNP sets extracted from a real GWAS dataset of non-small cell lung cancer in Han Chinese population. Simulation results show that when the MAF of the causal SNP is low, weighted principal component and weighted IBS are more powerful than PCA and other kernel machine functions at different LD structures and different numbers of causal SNPs. Application of the three methods to a real GWAS dataset indicates that wPCA and wIBS have better performance than the linear kernel, IBS kernel and PCA. more...
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- 2013
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24. Genetic variants at 12p11 and 12q24 are associated with breast cancer risk in a Chinese population.
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Zhenzhen Qin, Yanru Wang, Songyu Cao, Yisha He, Hongxia Ma, Guangfu Jin, Zhibin Hu, Xiaoxiang Guan, and Hongbing Shen
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Medicine ,Science - Abstract
BACKGROUND: A recent genome-wide association study (GWAS) has identified three new breast cancer susceptibility loci at 12p11, 12q24 and 21q21 in populations of European descent. However, because of the genetic heterogeneity, it is largely unknown for the role of these loci in the breast cancer susceptibility in the populations of non-European descent. METHODOLOGY/PRINCIPAL FINDINGS: Here, we genotyped three variants (rs10771399 at 12p11, rs1292011 at 12q24 and rs2823093 at 21q21) in an independent case-control study with a total of 1792 breast cancer cases and 1867 cancer-free controls in a Chinese population. We found that rs10771399 and rs1292011 were significantly associated with risk of breast cancer with per-allele odds ratios (ORs) of 0.85 (95% confidence interval (CI): 0.76-0.96; P = 0.010) and 0.84 (95% CI: 0.76-0.95; P = 4.50×10(-3)), respectively, which was consistent with those reported in populations of European descent. Similar effects were observed between ER/PR positive and negative breast cancer for both loci. However, we did not found significant association between rs2823093 and breast cancer risk (OR = 0.97, 95%CI = 0.76-1.24; P = 0.795). CONCLUSIONS/SIGNIFICANCE: Our results indicate that genetic variants at 12p11 and 12q24 may also play an important role in breast cancer development in Chinese women. more...
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- 2013
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25. A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure.
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Ruyang Zhang, Yang Zhao, Minjie Chu, Amar Mehta, Yongyue Wei, Yao Liu, Pengcheng Xun, Jianling Bai, Hao Yu, Li Su, Hongxi Zhang, Zhibin Hu, Hongbing Shen, Feng Chen, and David C Christiani
- Subjects
Medicine ,Science - Abstract
Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.Two SNPs were found to be significant (P more...
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- 2013
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26. SNP set association analysis for genome-wide association studies.
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Min Cai, Hui Dai, Yongyong Qiu, Yang Zhao, Ruyang Zhang, Minjie Chu, Juncheng Dai, Zhibin Hu, Hongbing Shen, and Feng Chen
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Medicine ,Science - Abstract
Genome-wide association study (GWAS) is a promising approach for identifying common genetic variants of the diseases on the basis of millions of single nucleotide polymorphisms (SNPs). In order to avoid low power caused by overmuch correction for multiple comparisons in single locus association study, some methods have been proposed by grouping SNPs together into a SNP set based on genomic features, then testing the joint effect of the SNP set. We compare the performances of principal component analysis (PCA), supervised principal component analysis (SPCA), kernel principal component analysis (KPCA), and sliced inverse regression (SIR). Simulated SNP sets are generated under scenarios of 0, 1 and ≥ 2 causal SNPs model. Our simulation results show that all of these methods can control the type I error at the nominal significance level. SPCA is always more powerful than the other methods at different settings of linkage disequilibrium structures and minor allele frequency of the simulated datasets. We also apply these four methods to a real GWAS of non-small cell lung cancer (NSCLC) in Han Chinese population. more...
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- 2013
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27. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers.
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Shengping Li, Ji Qian, Yuan Yang, Wanting Zhao, Juncheng Dai, Jin-Xin Bei, Jia Nee Foo, Paul J McLaren, Zhiqiang Li, Jingmin Yang, Feng Shen, Li Liu, Jiamei Yang, Shuhong Li, Shandong Pan, Yi Wang, Wenjin Li, Xiangjun Zhai, Boping Zhou, Lehua Shi, Xinchun Chen, Minjie Chu, Yiqun Yan, Jun Wang, Shuqun Cheng, Jiawei Shen, Weihua Jia, Jibin Liu, Jiahe Yang, Zujia Wen, Aijun Li, Ying Zhang, Guoliang Zhang, Xianrong Luo, Hongbo Qin, Minshan Chen, Hua Wang, Li Jin, Dongxin Lin, Hongbing Shen, Lin He, Paul I W de Bakker, Hongyang Wang, Yi-Xin Zeng, Mengchao Wu, Zhibin Hu, Yongyong Shi, Jianjun Liu, and Weiping Zhou more...
- Subjects
Genetics ,QH426-470 - Abstract
Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹⁹) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10⁻⁸), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻⁴; rs455804: OR = 0.84, P = 6.92×10⁻³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC. more...
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- 2012
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28. Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
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Jirong Long, Qiuyin Cai, Hyuna Sung, Jiajun Shi, Ben Zhang, Ji-Yeob Choi, Wanqing Wen, Ryan J Delahanty, Wei Lu, Yu-Tang Gao, Hongbing Shen, Sue K Park, Kexin Chen, Chen-Yang Shen, Zefang Ren, Christopher A Haiman, Keitaro Matsuo, Mi Kyung Kim, Ui Soon Khoo, Motoki Iwasaki, Ying Zheng, Yong-Bing Xiang, Kai Gu, Nathaniel Rothman, Wenjing Wang, Zhibin Hu, Yao Liu, Keun-Young Yoo, Dong-Young Noh, Bok-Ghee Han, Min Hyuk Lee, Hong Zheng, Lina Zhang, Pei-Ei Wu, Ya-Lan Shieh, Sum Yin Chan, Shenming Wang, Xiaoming Xie, Sung-Won Kim, Brian E Henderson, Loic Le Marchand, Hidemi Ito, Yoshio Kasuga, Sei-Hyun Ahn, Han Sung Kang, Kelvin Y K Chan, Hiroji Iwata, Shoichiro Tsugane, Chun Li, Xiao-Ou Shu, Dae-Hee Kang, and Wei Zheng more...
- Subjects
Genetics ,QH426-470 - Abstract
Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively. more...
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- 2012
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29. Genetic association analysis using sibship data: a multilevel model approach.
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Yang Zhao, Hao Yu, Ying Zhu, Monica Ter-Minassian, Zhihang Peng, Hongbing Shen, Nancy Diao, and Feng Chen
- Subjects
Medicine ,Science - Abstract
Family based association study (FBAS) has the advantages of controlling for population stratification and testing for linkage and association simultaneously. We propose a retrospective multilevel model (rMLM) approach to analyze sibship data by using genotypic information as the dependent variable. Simulated data sets were generated using the simulation of linkage and association (SIMLA) program. We compared rMLM to sib transmission/disequilibrium test (S-TDT), sibling disequilibrium test (SDT), conditional logistic regression (CLR) and generalized estimation equations (GEE) on the measures of power, type I error, estimation bias and standard error. The results indicated that rMLM was a valid test of association in the presence of linkage using sibship data. The advantages of rMLM became more evident when the data contained concordant sibships. Compared to GEE, rMLM had less underestimated odds ratio (OR). Our results support the application of rMLM to detect gene-disease associations using sibship data. However, the risk of increasing type I error rate should be cautioned when there is association without linkage between the disease locus and the genotyped marker. more...
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- 2012
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30. A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma.
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Yao Liu, Yixin Zhang, Juan Wen, Li Liu, Xiangjun Zhai, Jibin Liu, Shandong Pan, Jianguo Chen, Hongbing Shen, and Zhibin Hu
- Subjects
Medicine ,Science - Abstract
BACKGROUND: MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response and tumorigenesis. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. METHODS: We performed a case-control study including 1300 HBV-positive hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the association between rs999885 and the risk of HBV persistent infection and HCC. We also investigated the genotype-expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of HCC and adjacent non-tumor liver tissues. RESULTS: Compared with the HBV natural clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of 0.79 [95% confidence intervals (CIs) = 0.67-0.93]. However, the AG/GG genotypes were significantly associated with an increased HCC risk in HBV persistent carriers (adjusted OR = 1.25, 95% CIs = 1.06-1.47). Expression analysis revealed that the expression level of miR-106b-25 cluster was significantly higher in AG/GG carriers than those in AA carriers in non-tumor liver tissues. CONCLUSIONS: These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. more...
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- 2012
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31. HIV incidence and predictors associated with retention in a cohort of men who have sex with men in Yangzhou, Jiangsu Province, China.
- Author
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Zhihang Peng, Haitao Yang, Jessie Norris, Xin Chen, Xiping Huan, Rongbin Yu, Ning Wang, Hongbing Shen, and Feng Chen
- Subjects
Medicine ,Science - Abstract
BACKGROUND: The study was to investigate the incidence of HIV-1 and related factors, as well as predictors associated with retention in a cohort study among men who have sex with men (MSM) in Yangzhou, Jiangsu Province, China. A carefully designed 12-month prospective cohort study was conducted. METHODOLOGY/PRINCIPAL FINDINGS: A total of 278 sero-negative MSM were recruited and followed up for 12 months starting from May, 2008. Participants were tested for HIV-1 at baseline, 6-month, and 12-month follow-up visits. Questionnaire interviews were conducted to collect information. The retention rate and HIV incidence were analyzed as functions of demographic and behavioral variables. Risk factors were identified by estimating the relative risks (RR) and respective 95% confidence intervals (CI) using a Poisson regression model, univariate and multivariate analyses and risk factors analyses. 71 (25.5%) and 45 (16.2%) of the 278 participants were retained at the 6-month and 12-month follow-up visits respectively. The incidence rates of HIV-1 were 5.65 and 6.67 per 100 person years (PY) respectively. Both having received condoms and having received lubricant were negatively associated with HIV sero-conversion at the 12 months' follow-up. Predictors associated with 12-month retention rate include Yangzhou residency (RR=0.471, 95%CI: 0.275~0.807, P=0.006), having received condoms (RR=0.065, 95%CI: 0.007~0.572, P=0.014), and having received VCTs (RR=0.093, 95%CI: 0.010~0.818, P=0.032). CONCLUSIONS/SIGNIFICANCE: The incidence of HIV-1 among MSM in Yangzhou is relatively high and effective interventions are needed urgently. More attention should be focused on maintaining a higher retention rate. more...
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- 2012
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32. A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population.
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Yao Liu, Shandong Pan, Li Liu, Xiangjun Zhai, Jibin Liu, Juan Wen, Yixin Zhang, Jianguo Chen, Hongbing Shen, and Zhibin Hu
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk. METHODS: We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection. RESULTS: The variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68-0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65-1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance. CONCLUSIONS: The variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers. more...
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- 2012
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33. Genetic variations in key microRNA processing genes and risk of head and neck cancer: a case-control study in Chinese population.
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Hongxia Ma, Hua Yuan, Zhiyao Yuan, Chenjie Yu, Ruixia Wang, Yue Jiang, Zhibin Hu, Hongbing Shen, and Ning Chen
- Subjects
Medicine ,Science - Abstract
MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the miRNA-mRNA interactions, hence promoting tumorigenesis. In the present study, we hypothesized that potentially functional polymorphisms in miRNA processing genes may contribute to head and neck cancer (HNC) susceptibility. To test this hypothesis, we genotyped three SNPs at miRNA binding sites of miRNA processing genes (rs1057035 in 3'UTR of DICER, rs3803012 in 3'UTR of RAN and rs10773771 in 3'UTR of HIWI) with a case-control study including 397 HNC cases and 900 controls matched by age and sex in Chinese. Although none of three SNPs was significantly associated with overall risk of HNC, rs1057035 in 3'UTR of DICER was associated with a significantly decreased risk of oral cancer (TC/CC vs. TT: adjusted OR = 0.65, 95% CI = 0.46-0.92). Furthermore, luciferase activity assay showed that rs1057035 variant C allele led to significantly lower expression levels as compared to the T allele, which may be due to the relatively high inhibition of hsa-miR-574-3p on DICER mRNA. These findings indicated that rs1057035 located at 3'UTR of DICER may contribute to the risk of oral cancer by affecting the binding of miRNAs to DICER. Large-scale and well-designed studies are warranted to validate our findings. more...
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- 2012
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34. The study on newly developed McAb NJ001 specific to non-small cell lung cancer and its biological characteristics.
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Shiyang Pan, Fang Wang, Peijun Huang, Ting Xu, Lixia Zhang, Jian Xu, Qing Li, Wenying Xia, Ruihong Sun, Lei Huang, Ying Peng, Xuejun Qin, Yongqian Shu, Zhibin Hu, and Hongbing Shen
- Subjects
Medicine ,Science - Abstract
Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×10(6). The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical staining indicated that NJ001 could positively react to NSCLC, but weak positively or negatively react to human small-cell lung cancer (SCLC), pulmonary pseudotumor and other epithelial tumors. In soft agar assay, the colony formation efficiency in NJ001 groups decreased in a dose-dependent manner. For the concentration of 100 µg/ml, 200 µg/ml and 400 µg/ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition ratio in 200 µg, 400 µg and 800 µg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001 selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy for NSCLC and holds promise for further research regarding the mechanism underlying tumor progression of NSCLC. more...
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- 2012
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35. Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population.
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Yun Qian, Feng Lu, Meihua Dong, Yudi Lin, Huizhang Li, Jian Chen, Chong Shen, Guangfu Jin, Zhibin Hu, and Hongbing Shen
- Subjects
Medicine ,Science - Abstract
Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes.A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P more...
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- 2012
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36. Genetic variants at 1p11.2 and breast cancer risk: a two-stage study in Chinese women.
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Yue Jiang, Hao Shen, Xiao'an Liu, Juncheng Dai, Guangfu Jin, Zhenzhen Qin, Jiaping Chen, Shui Wang, Xinru Wang, Zhibin Hu, and Hongbing Shen
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Medicine ,Science - Abstract
BACKGROUND: Genome-wide association studies (GWAS) have identified several breast cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was reported to be associated with breast cancer in European populations. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage fine-mapping study with a total of 1792 breast cancer cases and 1867 controls. METHODOLOGY/PRINCIPAL FINDINGS: Seven single nucleotide polymorphisms (SNPs) including rs11249433 in a 277 kb region at 1p11.2 were selected and genotyping was performed by using TaqMan® OpenArray™ Genotyping System for stage 1 samples (878 cases and 900 controls). In stage 2 (914 cases and 967 controls), three SNPs (rs2580520, rs4844616 and rs11249433) were further selected and genotyped for validation. The results showed that one SNP (rs2580520) located at a predicted enhancer region of SRGAP2 was consistently associated with a significantly increased risk of breast cancer in a recessive genetic model [Odds Ratio (OR) = 1.66, 95% confidence interval (CI) = 1.16-2.36 for stage 2 samples; OR = 1.51, 95% CI = 1.16-1.97 for combined samples, respectively]. However, no significant association was observed between rs11249433 and breast cancer risk in this Chinese population (dominant genetic model in combined samples: OR = 1.20, 95% CI = 0.92-1.57). CONCLUSIONS/SIGNIFICANCE: Genotypes of rs2580520 at 1p11.2 suggest that Chinese women may have different breast cancer susceptibility loci, which may contribute to the development of breast cancer in this population. more...
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- 2011
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37. Evaluation of the association between the AC3 genetic polymorphisms and obesity in a Chinese Han population.
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Hairu Wang, Ming Wu, Weiguang Zhu, Jin Shen, Xiaoming Shi, Jie Yang, Qihui Zhao, Chuan Ni, Yaochu Xu, Hongbing Shen, Chong Shen, and Harvest F Gu
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Medicine ,Science - Abstract
BackgroundAC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight.Methodology/principal findingsIn the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5-23.9), 677 overweight (BMI 24.0-27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623-0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P(80)) and 455 controls (BMI = P(20-50)) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses.ConclusionsThe present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment. more...
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- 2010
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38. The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.
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Chao Agnes Hsiung, Qing Lan, Yun-Chul Hong, Chien-Jen Chen, H Dean Hosgood, I-Shou Chang, Nilanjan Chatterjee, Paul Brennan, Chen Wu, Wei Zheng, Gee-Chen Chang, Tangchun Wu, Jae Yong Park, Chin-Fu Hsiao, Yeul Hong Kim, Hongbing Shen, Adeline Seow, Meredith Yeager, Ying-Huang Tsai, Young Tae Kim, Wong-Ho Chow, Huan Guo, Wen-Chang Wang, Sook Whan Sung, Zhibin Hu, Kuan-Yu Chen, Joo Hyun Kim, Ying Chen, Liming Huang, Kyoung-Mu Lee, Yen-Li Lo, Yu-Tang Gao, Jin Hee Kim, Li Liu, Ming-Shyan Huang, Tae Hoon Jung, Guangfu Jin, Neil Caporaso, Dianke Yu, Chang Ho Kim, Wu-Chou Su, Xiao-Ou Shu, Ping Xu, In-San Kim, Yuh-Min Chen, Hongxia Ma, Min Shen, Sung Ick Cha, Wen Tan, Chin-Hao Chang, Jae Sook Sung, Mingfeng Zhang, Tsung-Ying Yang, Kyong Hwa Park, Jeff Yuenger, Chih-Liang Wang, Jeong-Seon Ryu, Yongbing Xiang, Qifei Deng, Amy Hutchinson, Jun Suk Kim, Qiuyin Cai, Maria Teresa Landi, Chong-Jen Yu, Ju-Yeon Park, Margaret Tucker, Jen-Yu Hung, Chien-Chung Lin, Reury-Perng Perng, Paolo Boffetta, Chih-Yi Chen, Kun-Chieh Chen, Shi-Yi Yang, Chi-Yuan Hu, Chung-Kai Chang, Joseph F Fraumeni, Stephen Chanock, Pan-Chyr Yang, Nathaniel Rothman, and Dongxin Lin more...
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Genetics ,QH426-470 - Abstract
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. more...
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- 2010
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39. Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
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Jirong Long, Qiuyin Cai, Xiao-Ou Shu, Shimian Qu, Chun Li, Ying Zheng, Kai Gu, Wenjing Wang, Yong-Bing Xiang, Jiarong Cheng, Kexin Chen, Lina Zhang, Hong Zheng, Chen-Yang Shen, Chiun-Sheng Huang, Ming-Feng Hou, Hongbing Shen, Zhibin Hu, Furu Wang, Sandra L Deming, Mark C Kelley, Martha J Shrubsole, Ui Soon Khoo, Kelvin Y K Chan, Sum Yin Chan, Christopher A Haiman, Brian E Henderson, Loic Le Marchand, Motoki Iwasaki, Yoshio Kasuga, Shoichiro Tsugane, Keitaro Matsuo, Kazuo Tajima, Hiroji Iwata, Bo Huang, Jiajun Shi, Guoliang Li, Wanqing Wen, Yu-Tang Gao, Wei Lu, and Wei Zheng more...
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Genetics ,QH426-470 - Abstract
Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures. more...
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- 2010
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40. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study
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Milan Savic, Stig E. Bojesen, David C. Christiani, Hans Brunnström, Rayjean J. Hung, Mattias Johansson, Maria Teresa Landi, Aage Haugen, Sungshim L. Park, Michael P.A. Davies, Jolanta Lissowska, Jian-Min Yuan, Demetrius Albanes, Mikael Johansson, Ivana Holcatova, James D. McKay, Jennifer A. Doherty, Geoffrey Liu, Kjell Grankvist, M. Dawn Teare, Ghislaine Scelo, Gad Rennert, Gary E. Goodman, Stephen Lam, Erik H.F.M. van der Heijden, Jonas Manjer, Adonina Tardón, Peter Kraft, Paul Brennan, Irene Brüske, Richard M. Martin, Neil E. Caporaso, Chu Chen, Yun-Chul Hong, Angeline S. Andrew, David Zaridze, W. Jay Christian, Kaitlin H Wade, Lambertus A. Kiemeney, Vladimir Janout, John K. Field, Michael W. Marcus, Melinda C. Aldrich, Caroline L Relton, Olle Melander, Philip C Haycock, Beata Swiatkowska, Dana Mates, Matthew B. Schabath, Eric J. Duell, Xifeng Wu, Susanne M. Arnold, Philip Lazarus, Ming-Sound Tsao, Christopher I. Amos, George Davey Smith, Hongbing Shen, Eric B. Haura, Loic Le Marchand, Heike Bickeböller, Robert Carreras-Torres, Penella J. Woll, Angela Risch, Anush Mukeriya, Nofer Institute of Occupational Medicine, Łódź, Poland, and Hu, Cheng more...
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0301 basic medicine ,Lung Neoplasms ,smoking habits ,Physiology ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lcsh:Medicine ,Genome-wide association study ,Bioinformatics ,Biochemistry ,Lung and Intrathoracic Tumors ,Body Mass Index ,Small Cell Lung Cancer ,Habits ,0302 clinical medicine ,Endocrinology ,Hàbit de fumar ,Polymorphism (computer science) ,Risk Factors ,Medicine and Health Sciences ,Smoking Habits ,Insulin ,2.1 Biological and endogenous factors ,Aetiology ,lcsh:Science ,Lung ,Cancer ,Likelihood Functions ,Multidisciplinary ,Mendelian Randomization Analysis ,Fasting ,Single Nucleotide ,Tobbacco habit ,Lipids ,3. Good health ,Phenotype ,Cholesterol ,Oncology ,Physiological Parameters ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,Physical Sciences ,ICEP ,Anatomy ,Lung cancer ,Statistics (Mathematics) ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Research Article ,Histology ,General Science & Technology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,BMI ,Insulin resistance ,Clinical Research ,Mendelian randomization ,Tobacco ,medicine ,Journal Article ,Confidence Intervals ,Genetics ,Humans ,Obesity ,Polymorphism ,Nutrition ,Diabetic Endocrinology ,Cancer och onkologi ,Behavior ,Tobacco Smoke and Health ,business.industry ,Prevention ,lcsh:R ,Body Weight ,Cancers and Neoplasms ,Biology and Life Sciences ,medicine.disease ,Hormones ,030104 developmental biology ,Cancer and Oncology ,Immunology ,Càncer de pulmó ,lcsh:Q ,Insulin Resistance ,business ,Body mass index ,Mathematics - Abstract
NCI, National Cancer Institute; NIHR, National Institute for Health Research, Carreras-Torres, R., Johansson, M., Haycock, P.C., Wade, K.H., Relton, C.L., Martin, R.M., Smith, G.D., Albanes, D., Aldrich, M.C., Andrew, A., Arnold, S.M., Bickeböller, H., Bojesen, S.E., Brunnström, H., Manjer, J., Brüske, I., Caporaso, N.E., Chen, C., Christiani, D.C., Christian, W.J., Doherty, J.A., Duell, E.J., Field, J.K., Davies, M.P.A., Marcus, M.W., Goodman, G.E., Grankvist, K., Haugen, A., Hong, Y.-C., Kiemeney, L.A., Van Der Heijden, E.H.F.M., Kraft, P., Johansson, M.B., Lam, S., Landi, M.T., Lazarus, P., Le Marchand, L., Liu, G., Melander, O., Park, S.L., Rennert, G., Risch, A., Haura, E.B., Scelo, G., Zaridze, D., Mukeriya, A., Savić, M., Lissowska, J., Swiatkowska, B., Janout, V., Holcatova, I., Mates, D., Schabath, M.B., Shen, H., Tardon, A., Teare, M.D., Woll, P., Tsao, M.-S., Wu, X., Yuan, J.-M., Hung, R.J., Amos, C.I., McKay, J., Brennan, P. more...
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- 2017
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41. Cumulative effect and predictive value of genetic variants associated with type 2 diabetes in Han Chinese: a case-control study
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Yudi Lin, Feng Lu, Juncheng Dai, Meihua Dong, H Li, Hongbing Shen, Guangfu Jin, Yun Qian, and Zhibin Hu
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Oncology ,Male ,Risk ,medicine.medical_specialty ,lcsh:Medicine ,Single-nucleotide polymorphism ,Genome-wide association study ,Type 2 diabetes ,Polymorphism, Single Nucleotide ,Asian People ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,lcsh:Science ,CDKAL1 ,Alleles ,Genetic association ,Genetics ,Multidisciplinary ,SLC30A8 ,biology ,business.industry ,lcsh:R ,Case-control study ,Odds ratio ,Middle Aged ,medicine.disease ,3. Good health ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,biology.protein ,Female ,lcsh:Q ,business ,Research Article - Abstract
Background Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We have previously confirmed the associations of genetic variants in HHEX, CDKAL1, VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes in Han Chinese are largely unknown. Methodology/Principal Findings We conducted a two-stage case-control study consisting of 2,925 cases and 3,281controls to examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio (OR) = 1.41, P = 9.91 × 10–16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34 × 10–10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 × 10-4 for rs1552224) and SLC30A8 (OR = 1.19, P = 1.43 × 10-5 for rs13266634). We further evaluated the cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or more risk alleles had a nearly 4-fold increased risk for developing type 2 diabetes compared with those carrying less than 6 risk alleles [adjusted OR = 3.68, 95% confidence interval (CI): 2.76–4.91]. Adding the genetic factors to clinical factors slightly improved the prediction of type 2 diabetes, with the area under the receiver operating characteristic curve increasing from 0.76 to 0.78. However, the difference was statistically significant (P < 0.0001). Conclusions/Significance We confirmed associations of SNPs in KCNQ1, CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The utilization of genetic information may improve the accuracy of risk prediction in combination with clinical characteristics for type 2 diabetes. more...
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- 2015
42. A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH
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Dongyang Chen, Zhihong Xu, Zheng Hao, Xiang Gao, Qing Jiang, Jin Dai, Ping Mao, Huajian Teng, Zhibin Hu, Ye Sun, Cheng Wang, Hongbing Shen, and Dongquan Shi
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Genotype ,lcsh:Medicine ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Risk Factors ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Allele ,lcsh:Science ,Hip Dislocation, Congenital ,Genotyping ,Genetics ,Multidisciplinary ,lcsh:R ,Case-control study ,Membrane Proteins ,Odds ratio ,Minor allele frequency ,Case-Control Studies ,lcsh:Q ,Genome-Wide Association Study ,Research Article - Abstract
Purpose Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH. Methods We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B). Results In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19–1.53) for allele A. Conclusion Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population. more...
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- 2015
43. Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer
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Yongmei Yin, Hongbing Shen, Zhibin Hu, Juncheng Dai, Jiaping Chen, Yue Jiang, Guangfu Jin, Zhenzhen Qin, Yanru Wang, Yisha He, and Hongxia Ma
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Oncology ,Epidemiology ,5' Flanking Region ,lcsh:Medicine ,Bioinformatics ,Breast Tumors ,Genotype ,3' Flanking Region ,lcsh:Science ,Multidisciplinary ,Obstetrics and Gynecology ,Genetic Epidemiology ,Medicine ,Female ,Cancer Epidemiology ,Research Article ,Risk ,medicine.medical_specialty ,Breast Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Molecular Genetics ,Breast cancer ,Internal medicine ,Breast Cancer ,Genetic variation ,Genetics ,Cancer Genetics ,Genetic predisposition ,medicine ,Humans ,Gene Regulation ,Genetic Predisposition to Disease ,Allele ,Alleles ,lcsh:R ,Case-control study ,Cancers and Neoplasms ,Genetic Variation ,Cancer ,medicine.disease ,MicroRNAs ,RNA processing ,Case-Control Studies ,Genetics of Disease ,Genetic Polymorphism ,lcsh:Q ,Gene expression ,Population Genetics - Abstract
Genetic variants in human microRNA (miRNA) genes may alter mature miRNA processing and/or target selection, and likely contribute to cancer susceptibility and disease progression. Previous studies have suggested that miR-101 may play important roles in the development of cancer by regulating key tumor-associated genes. However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in breast cancer susceptibility remains unclear. In this study, we genotyped 11 SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study of 1064 breast cancer cases and 1073 cancer-free controls. The results revealed that rs462480 and rs1053872 in the flank regions of pre-miR-101-2 were significantly associated with increased risk of breast cancer (rs462480 AC/CC vs AA: adjusted OR = 1.182, 95% CI: 1.030-1.357, P = 0.017; rs1053872 CG/GG vs CC: adjusted OR = 1.179, 95% CI: 1.040-1.337, P = 0.010). However, the remaining 9 SNPs were not significantly associated with risk of breast cancer. Additionally, combined analysis of the two high-risk SNPs revealed that subjects carrying the variant genotypes of rs462480 and rs1053872 had increased risk of breast cancer in a dose-response manner (P(trend) = 0.002). Compared with individuals with "0-1" risk allele, those carrying "2-4" risk alleles had 1.29-fold risk of breast cancer. In conclusion, these findings suggested that the SNPs rs462480 and rs1053872 residing in miR-101-2 gene may have a solid impact on genetic susceptibility to breast cancer, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis. more...
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- 2014
44. The spatial analysis on hemorrhagic fever with renal syndrome in Jiangsu province, China based on geographic information system
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Fenyang Tang, Zhihang Peng, Yefei Zhu, Feng Chen, Jianli Hu, Changjun Bao, Wanwan Liu, Ying Wu, Minghao Zhou, Wendong Liu, Yue-Jia Cheng, Rongbin Yu, Hongbing Shen, and Qi Liang
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Mainland China ,Cartography ,medicine.medical_specialty ,Veterinary medicine ,Computer and Information Sciences ,Viral Diseases ,China ,Geographic information system ,Spatial Epidemiology ,Endemic Diseases ,Epidemiology ,Prevalence ,lcsh:Medicine ,Plant Science ,Biology ,Disease Surveillance ,Infectious Disease Epidemiology ,Spatio-Temporal Analysis ,Risk Factors ,Environmental health ,Geoinformatics ,medicine ,Medicine and Health Sciences ,Cluster Analysis ,Humans ,lcsh:Science ,Multidisciplinary ,Population Biology ,Geography ,business.industry ,Public health ,Incidence (epidemiology) ,Incidence ,lcsh:R ,virus diseases ,Biology and Life Sciences ,Plant Pathology ,Infectious Diseases ,Hemorrhagic Fever with Renal Syndrome ,Epidemiological Monitoring ,Geographic Information Systems ,Earth Sciences ,lcsh:Q ,Public Health ,Endemic diseases ,business ,Research Article - Abstract
Background Hemorrhagic fever with renal syndrome (HFRS) is endemic in mainland China, accounting for 90% of total reported cases worldwide, and Jiangsu is one of the most severely affected provinces. In this study, the authors conducted GIS-based spatial analyses in order to determine the spatial distribution of the HFRS cases, identify key areas and explore risk factors for public health planning and resource allocation. Methods Interpolation maps by inverse distance weighting were produced to detect the spatial distribution of HFRS cases in Jiangsu from 2001 to 2011. Spatio-temporal clustering was applied to identify clusters at the county level. Spatial correlation analysis was conducted to detect influencing factors of HFRS in Jiangsu. Results HFRS cases in Jiangsu from 2001 to 2011 were mapped and the results suggested that cases in Jiangsu were not distributed randomly. Cases were mainly distributed in northeastern and southwestern Jiangsu, especially in Dafeng and Sihong counties. It was notable that prior to this study, Sihong county had rarely been reported as a high-risk area of HFRS. With the maximum spatial size of 50% of the total population and the maximum temporal size of 50% of the total population, spatio-temporal clustering showed that there was one most likely cluster (LLR = 624.52, P more...
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- 2014
45. Genetic variants at 12p11 and 12q24 are associated with breast cancer risk in a Chinese population
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Hongxia Ma, Yisha He, Guangfu Jin, Zhibin Hu, Songyu Cao, Yanru Wang, Xiaoxiang Guan, Hongbing Shen, and Zhenzhen Qin
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Oncology ,Genetic Screens ,Non-Clinical Medicine ,Epidemiology ,lcsh:Medicine ,Genome-wide association study ,Bioinformatics ,Risk Factors ,Genotype ,Odds Ratio ,lcsh:Science ,Multidisciplinary ,Cancer Risk Factors ,Medicine ,Female ,Cancer Epidemiology ,Research Article ,medicine.medical_specialty ,Genetic Causes of Cancer ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,Breast cancer ,Asian People ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Association Studies ,Chromosomes, Human, Pair 12 ,Health Care Policy ,Population Biology ,Genetic heterogeneity ,lcsh:R ,Case-control study ,Genetic variants ,Computational Biology ,Health Risk Analysis ,Human Genetics ,Odds ratio ,medicine.disease ,Confidence interval ,Biomarker Epidemiology ,Case-Control Studies ,Genetics of Disease ,Genetic Polymorphism ,lcsh:Q ,Population Genetics ,Genome-Wide Association Study - Abstract
BACKGROUND: A recent genome-wide association study (GWAS) has identified three new breast cancer susceptibility loci at 12p11, 12q24 and 21q21 in populations of European descent. However, because of the genetic heterogeneity, it is largely unknown for the role of these loci in the breast cancer susceptibility in the populations of non-European descent. METHODOLOGY/PRINCIPAL FINDINGS: Here, we genotyped three variants (rs10771399 at 12p11, rs1292011 at 12q24 and rs2823093 at 21q21) in an independent case-control study with a total of 1792 breast cancer cases and 1867 cancer-free controls in a Chinese population. We found that rs10771399 and rs1292011 were significantly associated with risk of breast cancer with per-allele odds ratios (ORs) of 0.85 (95% confidence interval (CI): 0.76-0.96; P = 0.010) and 0.84 (95% CI: 0.76-0.95; P = 4.50×10(-3)), respectively, which was consistent with those reported in populations of European descent. Similar effects were observed between ER/PR positive and negative breast cancer for both loci. However, we did not found significant association between rs2823093 and breast cancer risk (OR = 0.97, 95%CI = 0.76-1.24; P = 0.795). CONCLUSIONS/SIGNIFICANCE: Our results indicate that genetic variants at 12p11 and 12q24 may also play an important role in breast cancer development in Chinese women. more...
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- 2013
46. Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population
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Wei Wu, Feng Chen, Miaofei Xu, Chuncheng Lu, Yufeng Qin, Jian-Hua Qu, Ling Song, Zhibin Hu, Jiahao Sha, Shoulin Wang, Xinru Wang, Ying Wang, Hongbing Shen, and Yankai Xia
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Male ,Candidate gene ,China ,Genotype ,lcsh:Medicine ,Genome-wide association study ,Biology ,Bioinformatics ,urologic and male genital diseases ,Polymorphism, Single Nucleotide ,Male infertility ,Asian People ,Gene Frequency ,Genetic variation ,medicine ,Humans ,Exome ,Genetic Predisposition to Disease ,lcsh:Science ,Allele frequency ,Alleles ,Azoospermia ,Genetics ,Multidisciplinary ,lcsh:R ,Case-control study ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Oligospermia ,medicine.disease ,Case-Control Studies ,lcsh:Q ,Genome-Wide Association Study ,Research Article - Abstract
BACKGROUND: Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA). OBJECTIVE: To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia. DESIGN SETTING AND PARTICIPANTS: A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011. MEASUREMENTS: We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping. RESULTS AND LIMITATIONS: Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P = 0.005, 95%CI 1.58-13.4) and 1.82 (P = 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings. CONCLUSIONS: Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future. more...
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- 2013
47. Pathway analysis for genome-wide association study of lung cancer in Han Chinese population
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Jianwei Gou, Tangchun Wu, Minjie Chu, Chen Wu, Feng Chen, Ruyang Zhang, Dongxin Lin, Zhibin Hu, Yang Zhao, Hongbing Shen, Chen Qian, Juncheng Dai, Guangfu Jin, Lingmin Hu, Cheng Wang, and Jianling Bai more...
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Male ,Lung Neoplasms ,lcsh:Medicine ,Genome-wide association study ,medicine.disease_cause ,0302 clinical medicine ,lcsh:Science ,Genetics ,0303 health sciences ,Multidisciplinary ,Cancer Risk Factors ,Genomics ,3. Good health ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Female ,Algorithms ,Research Article ,Signal Transduction ,Risk ,China ,Genetic Causes of Cancer ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genome Analysis Tools ,medicine ,Genome-Wide Association Studies ,Humans ,Genetic Predisposition to Disease ,KEGG ,Lung cancer ,Gene ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Population Biology ,Models, Genetic ,lcsh:R ,Case-control study ,Computational Biology ,Human Genetics ,medicine.disease ,Case-Control Studies ,Multiple comparisons problem ,Genetic Polymorphism ,lcsh:Q ,Carcinogenesis ,Population Genetics ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) have identified a number of genetic variants associated with lung cancer risk. However, these loci explain only a small fraction of lung cancer hereditability and other variants with weak effect may be lost in the GWAS approach due to the stringent significance level after multiple comparison correction. In this study, in order to identify important pathways involving the lung carcinogenesis, we performed a two-stage pathway analysis in GWAS of lung cancer in Han Chinese using gene set enrichment analysis (GSEA) method. Predefined pathways by BioCarta and KEGG databases were systematically evaluated on Nanjing study (Discovery stage: 1,473 cases and 1,962 controls) and the suggestive pathways were further to be validated in Beijing study (Replication stage: 858 cases and 1,115 controls). We found that four pathways (achPathway, metPathway, At1rPathway and rac1Pathway) were consistently significant in both studies and the P values for combined dataset were 0.012, 0.010, 0.022 and 0.005 respectively. These results were stable after sensitivity analysis based on gene definition and gene overlaps between pathways. These findings may provide new insights into the etiology of lung cancer. more...
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- 2013
48. Weighted SNP set analysis in genome-wide association study
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Minjie Chu, Feng Chen, Min Cai, Hui Dai, Ruyang Zhang, Zhibin Hu, Juncheng Dai, Yang Zhao, Hongbing Shen, and Cheng Qian
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lcsh:Medicine ,Single-nucleotide polymorphism ,Genome-wide association study ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Asian People ,Gene Frequency ,Carcinoma, Non-Small-Cell Lung ,Humans ,lcsh:Science ,Allele frequency ,Genetic association ,Genetics ,Principal Component Analysis ,Multidisciplinary ,Models, Genetic ,lcsh:R ,Minor allele frequency ,Kernel method ,Kernel (statistics) ,Data Interpretation, Statistical ,Principal component analysis ,lcsh:Q ,Genome-Wide Association Study ,Research Article - Abstract
Genome-wide association studies (GWAS) are popular for identifying genetic variants which are associated with disease risk. Many approaches have been proposed to test multiple single nucleotide polymorphisms (SNPs) in a region simultaneously which considering disadvantages of methods in single locus association analysis. Kernel machine based SNP set analysis is more powerful than single locus analysis, which borrows information from SNPs correlated with causal or tag SNPs. Four types of kernel machine functions and principal component based approach (PCA) were also compared. However, given the loss of power caused by low minor allele frequencies (MAF), we conducted an extension work on PCA and used a new method called weighted PCA (wPCA). Comparative analysis was performed for weighted principal component analysis (wPCA), logistic kernel machine based test (LKM) and principal component analysis (PCA) based on SNP set in the case of different minor allele frequencies (MAF) and linkage disequilibrium (LD) structures. We also applied the three methods to analyze two SNP sets extracted from a real GWAS dataset of non-small cell lung cancer in Han Chinese population. Simulation results show that when the MAF of the causal SNP is low, weighted principal component and weighted IBS are more powerful than PCA and other kernel machine functions at different LD structures and different numbers of causal SNPs. Application of the three methods to a real GWAS dataset indicates that wPCA and wIBS have better performance than the linear kernel, IBS kernel and PCA. more...
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- 2013
49. Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer
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Ronald Herbst, Heng Zhao, Lihua Huang, Haihong Zhong, Baohui Han, Philip Brohawn, Song Wu, Xin Yao, Sarah Conley, Dong Shen, Yinong Sebastian, Yihong Yao, Yanjie Niu, Brandon W. Higgs, Wei Zhang, Zhibin Hu, David A. Tice, Wei Zhu, Bahija Jallal, Meggan Czapiga, Yizhuo Zhao, Katie Streicher, Zheng Liu, Meng Zhu, Jiaqi Huang, Vaheh Oganesyan, Xinying Su, Haihua Fu, Hongbing Shen, Xiaoxiao Ge, Yi Gu, Yue Jiang, Shyoung Li, Lin Xu, Yuqing Lou, Zhan Xiao, Liyan Jiang, Jianren Gu, and Chris Morehouse more...
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Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Carcinogenesis ,Cancer Treatment ,Bioinformatics ,medicine.disease_cause ,Biochemistry ,Lung and Intrathoracic Tumors ,Transcriptome ,Small Cell Lung Cancer ,Medicine and Health Sciences ,Ethnicities ,Small interfering RNAs ,Carcinoma, Small Cell ,Genetics (clinical) ,Exome sequencing ,Oncogene Proteins ,Mutation ,Serine-Arginine Splicing Factors ,Middle Aged ,humanities ,Nucleic acids ,Oncology ,Female ,Research Article ,Adult ,lcsh:QH426-470 ,DNA Copy Number Variations ,DNA repair ,Biology ,03 medical and health sciences ,Genetics ,medicine ,Carcinoma ,Humans ,Gene Silencing ,Non-coding RNA ,neoplasms ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Aged ,Biology and life sciences ,Cancers and Neoplasms ,Human Genetics ,DNA ,medicine.disease ,Human genetics ,Gene regulation ,respiratory tract diseases ,lcsh:Genetics ,030104 developmental biology ,People and Places ,Cancer research ,RNA ,Population Groupings ,Gene expression ,Chinese People ,DNA Damage - Abstract
Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC., Author Summary SCLC patients are initially highly chemo-sensitive with response rates of greater than 80% in both limited and extensive diseases, but suffer uniform disease recurrence or progression in a very short period of time. In the absence of well-defined genomic biomarkers and insights into the resistance mechanism, many targeted treatments have yielded negative results in the last decade Using integrated next generation sequencing (NGS) technology in combination with a high quality surgical sample set with comprehensive clinical annotation, our study not only identified novel recurrent genetic alterations in genes such as CDH10 and DNA repair pathways which may influence outcomes in SCLC patients, but also discovered the expression of SRSF1, an RNA-splicing factor which can both regulate key oncogenic and survival pathways such as BCL2, and play a critical role in patient survival. more...
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- 2016
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50. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers
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Xiangjun Zhai, Li Jin, Xinchun Chen, Yuan Yang, Meng-Chao Wu, Paul J. McLaren, Jiawei Shen, Guoliang Zhang, Wei Hua Jia, Zhiqiang Li, Jia Nee Foo, Boping Zhou, Hongbing Shen, Zhibin Hu, Jun Wang, Jianjun Liu, S. W. Li, Jibin Liu, Shandong Pan, Yongyong Shi, Yi-Qun Yan, Yi Wang, Yi Xin Zeng, Paul I.W. de Bakker, Jingmin Yang, Hongyang Wang, Wenjin Li, Juncheng Dai, Feng Shen, Hua Wang, Ai-jun Li, Shengping Li, Ying Zhang, Minshan Chen, Jin Xin Bei, Lehua Shi, Jia-mei Yang, Dongxin Lin, Zujia Wen, Ji Qian, Xianrong Luo, Jiahe Yang, Weiping Zhou, Minjie Chu, Lin He, Wanting Zhao, Shu-Qun Cheng, Li Liu, and Hongbo Qin more...
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Adult ,Male ,Oncology ,Hepatitis B virus ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,lcsh:QH426-470 ,Genome-wide association study ,Single-nucleotide polymorphism ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,HLA-DQ alpha-Chains ,Virus ,Receptors, Kainic Acid ,Internal medicine ,Heredity ,Cancer Genetics ,Genome-Wide Association Studies ,Genetics ,medicine ,GRIK1 ,Humans ,Genetic Predisposition to Disease ,Biology ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Genetic association ,biology ,Liver Neoplasms ,Middle Aged ,medicine.disease ,digestive system diseases ,lcsh:Genetics ,Hepatocellular carcinoma ,biology.protein ,Female ,Research Article ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10−19) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10−8), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10−4; rs455804: OR = 0.84, P = 6.92×10−3). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC., Author Summary Previous studies strongly suggest the importance of genetic susceptibility for hepatocellular carcinoma (HCC). However, the studies about genetic etiology on HBV–related HCC were limited. Our genome-wide association study included 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers for the discovery analysis. 2,112 HBV–positive HCC cases and 2,208 HBV carriers (the initial validation), and 1,021 cases and 1,491 HBV carriers (the second validation), were then analyzed for validation. The fourth independent samples of 1,298 cases and 1,026 controls were analyzed as replication. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 and rs455804 (GRIK1) on 21q21.3. HLA-DRB1 molecules play an important role in chronic HBV infection and progression to HCC. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC. more...
- Published
- 2012
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