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Pancreatic Neoplasms: HELP
Articles by Guo-Liang Jiang
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, Guoliang Jiang wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. 2014

Wang, Zheng / Lai, Song-Tao / Xie, Li / Zhao, Jian-Dong / Ma, Ning-Yi / Zhu, Ji / Ren, Zhi-Gang / Jiang, Guo-Liang. ·Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. · Department of Statistics, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Statistics, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhigang-ren@163.com. ·Diabetes Res Clin Pract · Pubmed #24837144.

ABSTRACT: AIMS: Recent epidemiological studies indicated that use of metformin might decrease the risk of various cancers among patients with type 2 diabetes mellitus (T2DM). However, its influence on pancreatic cancer was controversial. Therefore, we did a meta-analysis of currently available observational studies on the issue. METHODS: We did a PubMed and ISI Web of Science search for observational articles. The pooled relative risk (RR) was estimated using a random-effect model. Heterogeneity was evaluated using I(2) statistic. Subgroup analysis was performed to explore the source of heterogeneity and confirm the overall estimates. Publication bias was also examined. RESULTS: The analysis included 11 articles (13 studies) comprising 10 cohort studies and 3 case-control studies. Use of metformin was associated with a significant lower risk of pancreatic cancer [RR 0.63, 95% confidence internal (CI) 0.46-0.86, p=0.003]. In a total 11 subgroup analyses, 5 provided the consistent result with pooled effect estimates of overall analysis. No publication bias was detected by Begg's (Z=-0.79, p=0.428) and Egger's test (t=-0.92, p=0.378). CONCLUSIONS: From present observational studies, use of metformin appears to be associated with a reduced risk of pancreatic cancer in patients with T2DM. Further investigation is needed.

2 Clinical Trial Intensity modulated radiotherapy for locally advanced and metastatic pancreatic cancer: a mono-institutional retrospective analysis. 2015

Wang, Zheng / Ren, Zhi-Gang / Ma, Ning-Yi / Zhao, Jian-Dong / Zhang, Zhen / Ma, Xue-Jun / Long, Jiang / Xu, Jin / Jiang, Guo-Liang. ·Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. drwangzheng@hotmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. drwangzheng@hotmail.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. zhigang-ren@163.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. zhigang-ren@163.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. many_fdu@hotmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. many_fdu@hotmail.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. neilzhaojiandong@gmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. neilzhaojiandong@gmail.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. zhenzhang6@gmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. zhenzhang6@gmail.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. chateauma99@gmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. chateauma99@gmail.com. · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. surgeonlong@hotmail.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. surgeonlong@hotmail.com. · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. xjuin@163.com. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. xjuin@163.com. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, China. guoliang.jiang@sphic.org.cn. · Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China. guoliang.jiang@sphic.org.cn. · Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, 4365 Kangxin Road, Shanghai, 201321, China. guoliang.jiang@sphic.org.cn. ·Radiat Oncol · Pubmed #25575617.

ABSTRACT: BACKGROUND: To evaluate the role of intensity modulated radiotherapy (IMRT) for locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), and the prognostic factors in the setting of multidisciplinary approach strategies. METHODS: 63 patients with LAPC and MPC receiving IMRT in our institution were retrospectively identified. Information on patient baseline, treatment characteristics and overall survival (OS) time were collected. Data of pain relief and toxicity were evaluated. Univariate and multivariate analyses were conducted to investigate the prognostic factors. RESULTS: All patients received IMRT with a median dose of 46.0 Gy. The median OS for LAPC and MPC patients were 15.7 months and 8.0 months, respectively (p = 0.029). Symptomatic improvements were observed in the 44 patients with abdominal/back pain after radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in those with severe pain. Only 13.9% and 14.8% cases presented Grade ≥ 3 hematologic toxicities in RT and CCRT group, while no cases developed Grade ≥ 3 non-hematologic toxicities in both groups. Multivariate analysis indicated that tumors located in pancreas body/tail (HR 0.28, p = 0.008), pretreatment CA19-9 < 1000 U/mL (HR 0.36, p = 0.029) and concurrent chemotherapy (HR 0.37, p = 0.016) were independent favorable predictors for OS. CONCLUSIONS: CCRT further improved OS for LAPC and MPC with acceptable toxicities, and use of RT markedly alleviated pain. Tumors located in pancreas body/tail, pretreatment CA19-9 level of < 1000 U/mL and CCRT were associated with better OS. However, regional intra-arterial chemotherapy did not show any survival benefit in our study.

3 Article Evaluating dosimetric constraints for carbon ion radiotherapy in the treatment of locally advanced pancreatic cancer. 2020

Lin, Lien-Chun / Jiang, Guo-Liang / Ohri, Nitin / Wang, Zheng / Lu, Jiade J / Garg, Madhur / Guha, Chandan / Wu, Xiaodong. ·Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, 4365 Kangxin Road, Shanghai, 201318, China. · Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China. · Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, 111 E 210th St, Bronx, NY, 10467, USA. · Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, 111 E 210th St, Bronx, NY, 10467, USA. cguha@montefiore.org. · Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, 4365 Kangxin Road, Shanghai, 201318, China. drxiaodongwu@yahoo.com. ·Radiat Oncol · Pubmed #32381042.

ABSTRACT: OBJECTIVE: To identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC). METHODS: We generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE × 12, 4.0 GyRBE × 14, and 3.0 GyRBE × 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk. RESULTS: Using 4.6 GyRBE × 12 and 4.0 GyRBE × 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE × 17. Low-dose constraints could not uniformly be achieved using any dose schedule. CONCLUSION: While selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE × 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE × 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.

4 Article Proton and carbon ion radiation therapy for locally advanced pancreatic cancer: A phase I dose escalation study. 2020

Yu, Zhan / Hong, Zhengshan / Zhang, Qing / Lin, Lien-Chun / Shahnazi, Kambiz / Wu, Xiaodong / Lu, Jiade / Jiang, Guoliang / Wang, Zheng. ·Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China. · Department of Radiation Physics, Shanghai Proton and Heavy Ion Center, Shanghai, China. · Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. · Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China. Electronic address: zheng.wang@sphic.org.cn. ·Pancreatology · Pubmed #32033896.

ABSTRACT: OBJECTIVE: To determine the maximum tolerated dose (MTD) of proton and carbon ion radiation therapy (PCRT) for locally advanced pancreatic cancer (LAPC). METHODS: A single-institution, phase I dose escalation study was performed. The proton dose of 50.4 GyE in 28 fractions was delivered to clinical target volume, and carbon ion as a boost dose to gross tumor volume escalated from 12 GyE to 18 GyE with 3 GyE per fraction in 3 dose levels. The dose limiting toxicity (DLT) was defined as any treatment-related grade (G)3 or higher of non-hematological toxicity. The MTD was exceeded if ≥2 patients in a dose level developed DLT. RESULTS: From May 2015 to July 2016, ten patients were enrolled, 3 in dose level 1, 4 in dose level 2, and 3 in dose level 3. With a median follow-up of 17.4 months, no patient developed a DLT, and the acute G1-2 of gastrointestinal (GI) and hepatic toxicity occurred in 40% of patients, and G1 of GI late toxicity, in 30%. The median overall survival was 17.3 months. CONCLUSION: Higher than 50.4 GyE could be given by PCRT with slight toxicity and good tolerance for LAPC, and the tumor control and survival had been improved, but not significantly. Better outcome may be achieved using carbon ion radiation therapy with higher biological equivalent dose.

5 Article Improved Survival in Patients with Resected Pancreatic Carcinoma Using Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial Infusion Chemotherapy. 2017

Ma, Ningyi / Wang, Zheng / Zhao, Jiandong / Long, Jiang / Xu, Jin / Ren, Zhigang / Jiang, Guoliang. ·Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China (mainland). · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China (mainland). ·Med Sci Monit · Pubmed #28512284.

ABSTRACT: BACKGROUND We assessed the role of adjuvant intensity-modulated radiotherapy (IMRT) in combination with chemotherapy for pancreatic carcinomas after curative resection and identified prognostic factors related to pancreatic carcinoma after multidisciplinary treatment strategies. MATERIAL AND METHODS Pancreatic carcinoma patients (n=61) who received adjuvant radiotherapy after resection (median dose, 50.4 Gy) between 2010 and 2016 were retrospectively identified. Sixty patients received chemotherapy, including concurrent chemoradiotherapy (CCRT), systemic chemotherapy, and regional intra-arterial infusion chemotherapy (RIAC). The Kaplan-Meier method was used to measure the 3-year overall survival (OS) and disease-free survival (DFS) rates. Log-rank univariate analysis and multivariate Cox regression model analysis were used to identify prognostic factors. RESULTS Median follow-up time was 25.5 (range, 4.9-59.7) months. The 3-year OS and DFS rates were 31.0% and 16.1%, respectively. The median OS and DFS were 27.4 and 16.7 months, respectively. Multivariate analysis indicated that independent favorable predictors for OS were CCRT (p=0.039) and postoperative RIAC (p=0.044). Moreover, postoperative RIAC (p=0.027), and pre-radiotherapy CA19-9 ≤37 U/mL (p=0.0080) were independent favorable predictors for DFS. The combination of radiotherapy and chemotherapy was tolerated well by the patients, and no treatment-related death occurred. CONCLUSIONS Combined IMRT and adjuvant chemotherapy appeared safe and effective for pancreatic carcinoma. CCRT was associated with improved survival with acceptable toxicity. We propose that radiotherapy could be a part of postoperative treatment, but it should be administered concurrently with chemotherapy. Adding RIAC was associated with improved OS and DFS and it could be integrated into the postoperative treatment regimen.

6 Article Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation. 2016

Zheng, Jian / Huang, Xudong / Tan, Wen / Yu, Dianke / Du, Zhongli / Chang, Jiang / Wei, Lixuan / Han, Yaling / Wang, Chengfeng / Che, Xu / Zhou, Yifeng / Miao, Xiaoping / Jiang, Guoliang / Yu, Xianjun / Yang, Xianghong / Cao, Guangwen / Zuo, Chaohui / Li, Zhaoshen / Wang, Chunyou / Cheung, Siu Tim / Jia, Yongfeng / Zheng, Xiongwei / Shen, Hongbing / Wu, Chen / Lin, Dongxin. ·State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Genetics, Medical College of Soochow University, Suzhou, China. · School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. · Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, China. · Department of Pancreas and Hepatobiliary Surgery, Cancer Hospital, Fudan University, Shanghai, China. · Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, China. · Department of Epidemiology, Second Military Medical University, Shanghai, China. · Department of Gastroduodenal and Pancreatic Surgery, Hunan Province Tumor Hospital, Changsha, China. · Department of Gastroenterology, First Affiliated Hospital, Second Military Medical University, Shanghai, China. · Union Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. · Department of Surgery, University of Hong Kong, Hong Kong, China. · Department of Pathology, Affiliated Hospital, Inner Mongolia School of Medicine, Huhhot, China. · Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China. · Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China. · Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. ·Nat Genet · Pubmed #27213290.

ABSTRACT: Genome-wide association studies have identified several loci associated with pancreatic cancer risk; however, the mechanisms by which genetic factors influence the development of sporadic pancreatic cancer remain largely unknown. Here, by using genome-wide association analysis and functional characterization, we identify a long intergenic noncoding RNA (lincRNA), LINC00673, as a potential tumor suppressor whose germline variation is associated with pancreatic cancer risk. LINC00673 is able to reinforce the interaction of PTPN11 with PRPF19, an E3 ubiquitin ligase, and promote PTPN11 degradation through ubiquitination, which causes diminished SRC-ERK oncogenic signaling and enhanced activation of the STAT1-dependent antitumor response. A G>A change at rs11655237 in exon 4 of LINC00673 creates a target site for miR-1231 binding, which diminishes the effect of LINC00673 in an allele-specific manner and thus confers susceptibility to tumorigenesis. These findings shed new light on the important role of LINC00673 in maintaining cell homeostasis and how its germline variation might confer susceptibility to pancreatic cancer.

7 Article Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2 checkpoint and inhibiting DNA damage repair. 2015

Wang, Zheng / Lai, Song-Tao / Ma, Ning-Yi / Deng, Yun / Liu, Yong / Wei, Dong-Ping / Zhao, Jian-Dong / Jiang, Guo-Liang. ·Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China. · Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China. · Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, 4365 Kangxin Road, Shanghai 201321, China. Electronic address: guoliang.jiang@sphic.org.cn. ·Cancer Lett · Pubmed #26304716.

ABSTRACT: Recent evidences have demonstrated the potential of metformin as a novel agent for cancer prevention and treatment. Here, we investigated its ability of radiosensitization and the underlying mechanisms in human pancreatic cancer cells. In this study, we found that metformin at 5 mM concentration enhanced the radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation. Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by γ-H2AX and 53BP1 signaling. Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Our data suggest that metformin radiosensitizes pancreatic cancer cells in vitro via abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the in vivo study is needed to further confirm the findings from the in vitro study.

8 Article Genome-wide association study of survival in patients with pancreatic adenocarcinoma. 2014

Wu, Chen / Kraft, Peter / Stolzenberg-Solomon, Rachael / Steplowski, Emily / Brotzman, Michelle / Xu, Mousheng / Mudgal, Poorva / Amundadottir, Laufey / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / Kooperberg, Charles / Petersen, Gloria M / Zheng, Wei / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Cao, Guangwen / Duell, Eric J / Elena, Joanne W / Gaziano, J Michael / Giovannucci, Edward L / Hallmans, Goran / Hutchinson, Amy / Hunter, David J / Jenab, Mazda / Jiang, Guoliang / Khaw, Kay-Tee / LaCroix, Andrea / Li, Zhaoshen / Mendelsohn, Julie B / Panico, Salvatore / Patel, Alpa V / Qian, Zhi Rong / Riboli, Elio / Sesso, Howard / Shen, Hongbing / Shu, Xiao-Ou / Tjonneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chengfeng / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen / Hoover, Robert / Hartge, Patricia / Fuchs, Charles S / Lin, Dongxin / Wolpin, Brian M. ·Department of Epidemiology, Harvard School of Public Health, , Boston, Massachusetts, USA. ·Gut · Pubmed #23180869.

ABSTRACT: BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

9 Article Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer. 2013

Huang, Liming / Wu, Chen / Yu, Dianke / Wang, Chengfeng / Che, Xu / Miao, Xiaoping / Zhai, Kan / Chang, Jiang / Jiang, Guoliang / Yang, Xianghong / Cao, Guangwen / Hu, Zhibin / Zhou, Yongjian / Zuo, Chaohui / Wang, Chunyou / Zhang, Xianghong / Zhou, Yifeng / Yu, Xianjun / Dai, Wanjin / Li, Zhaoshen / Shen, Hongbing / Liu, Luming / Chen, Yanling / Zhang, Sheng / Wang, Xiaoqi / Liu, Yu / Sun, Menghong / Cao, Wei / Gao, Jun / Ma, Ying / Zheng, Xiongwei / Cheung, Siu Tim / Jia, Yongfeng / Tan, Wen / Wu, Tangchun / Lin, Dongxin. ·State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ·Carcinogenesis · Pubmed #23299404.

ABSTRACT: Germline mutations in genes that cause hereditary syndromes are highly predisposed to familial pancreatic cancer. However, genetic susceptibility to sporadic pancreatic cancer is largely uncovered. We conducted a two-stage association study on pancreatic cancer that included 981 cases and 1991 controls in the first stage followed by a second stage (2603 cases and 2877 controls). Using an approach based on candidate genes whose roles in pancreatic cancer have been well known, we identified two new susceptibility loci. rs11571836 located in the BRCA2 3'-untranslated region was significantly associated with lower expression of BRCA2 transcript and increased pancreatic cancer risk [odds ratio = 1.30, 95% confidence interval = 1.14-1.47, P = 7.64 × 10(-5)] in a recessive manner. rs12939944 located in the MAP2K4 intron was associated with decreased risk (odds ratio = 0.82, 95% confidence interval = 0.74-0.91, P = 0.0001) in a dominant manner. Our results demonstrate for the first time that common variants in BRCA2 and MAP2K4 are susceptibility to sporadic pancreatic cancer.

10 Article Copy number variation at 6q13 functions as a long-range regulator and is associated with pancreatic cancer risk. 2012

Huang, Liming / Yu, Dianke / Wu, Chen / Zhai, Kan / Jiang, Guoliang / Cao, Guangwen / Wang, Chunyou / Liu, Yu / Sun, Menghong / Li, Zhaoshen / Tan, Wen / Lin, Dongxin. ·State Key Laboratory of Molecular Oncology and Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. ·Carcinogenesis · Pubmed #22016467.

ABSTRACT: Copy number variations (CNVs) have been recognized to contribute to phenotypic variations and to be associated with susceptibility to certain complex diseases. This study examined the functional significance of CNVR2966.1 at 6q13 and its association with pancreatic cancer susceptibility. The CNVR2966.1 was found to be a 10,379 bp nucleotides deletion/insertion within the uniform boundaries chromosome 6: 74 648 791-74 659 169. Luciferase reporter gene assays revealed an active regulator in CNVR2966.1, which was demonstrated by circular chromosome conformation capture assays to physically interact with the upstream functional sequence of CDKN2B. CDKN2B transcription levels in pancreatic tissues were therefore significantly higher in individuals with two copies of CNVR2966.1 than in those with low copy number of CNVR2966.1. The risk of pancreatic cancer observed in 1027 cases and 1031 controls was significantly associated with copy number of CNVR2966.1, with the odds ratio being 1.31 (95% confidence interval = 1.08-1.60; P = 0.007) for one copy genotype compared with two copies genotype. These results suggest that CNVR2966.1 is associated with pancreatic cancer risk probably owing to its effect on long-range regulation of CDKN2B.

11 Article Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. 2011

Wu, Chen / Miao, Xiaoping / Huang, Liming / Che, Xu / Jiang, Guoliang / Yu, Dianke / Yang, Xianghong / Cao, Guangwen / Hu, Zhibin / Zhou, Yongjian / Zuo, Chaohui / Wang, Chunyou / Zhang, Xianghong / Zhou, Yifeng / Yu, Xianjun / Dai, Wanjin / Li, Zhaoshen / Shen, Hongbing / Liu, Luming / Chen, Yanling / Zhang, Sheng / Wang, Xiaoqi / Zhai, Kan / Chang, Jiang / Liu, Yu / Sun, Menghong / Cao, Wei / Gao, Jun / Ma, Ying / Zheng, Xiongwei / Cheung, Siu Tim / Jia, Yongfeng / Xu, Jian / Tan, Wen / Zhao, Ping / Wu, Tangchun / Wang, Chengfeng / Lin, Dongxin. ·State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ·Nat Genet · Pubmed #22158540.

ABSTRACT: Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10(-13) to P = 4.18 × 10(-10)) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.