机构:[1]Division of Cancer Epidemiology and Genetics [2]Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, [3]Core Genotyping Facility, NCI-Frederick, SAIC-Frederick, Frederick, MD, USA, [4]Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan 453003, China, [5]Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital [6]Department of Basic Oncology and Pathology, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China, [7]Department of Thoracic Surgery and Tumor Prevention Treatment, Anyang Tumor Hospital, Anyang, Henan 455000, China, [8]Department of Pathology and Thoracic Surgery, Centre for Health Screening and Endoscopy, Cixian Hospital, Cixian, Hebei 056500, China, [9]Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA, [10]University of Pittsburgh Cancer Institute, Pittsburg, PA, USA, [11]Shanxi Cancer Hospital, Taiyuan, Shanxi, China, [12]Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, China, [13]Shanghai Cancer Institute, Shanghai, China, [14]Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore, [15]Information Management Services, Inc., Silver Spring, MD, USA, [16]Department of Thoracic Surgery, Tumor Hospital of Linzhou, Linzhou, Henan 456550, China, [17]Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China, [18]Institute of Hematologic Disease and Department of Pathology, Changzhi Medical University, Changzhi, Shanxi 046000, China, [19]Department of Pathology and Thoracic Surgery, Linzhou Esophageal Cancer Hospital, Linzhou, Henan 456592, China, [20]Department of Oncology, The First Affiliated Hospital of Nanyang Medical College, Nanyang, Henan 473058, China, [21]Department of Oncology, The First People’s Hospital of Hebi, Hebi, Henan 458000, China, [22]Department of Biostatistics, Hebi City Public Health Bureau, Hebi, Henan 458000, China, [23]Qixian Commerce Bureau, Hebi, Henan 456750, China, [24]Department of Oncology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, China, [25]Department of Gastroenterology and Thoracic Surgery, The First People’s Hospital of Shangqiu, Shangqiu, Henan 476100, China, [26]Department of Radiotherapy, Xinxiang Central Hospital, Xinxiang, Henan 453000, China, [27]Department of Surgery, Hebi Dahejian Hospital, Hebi, Henan 458000, China, [28]Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China, [29]Department of Thoracic Surgery and Radiotherapy, Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China, 河南省肿瘤医院[30]Department of Gastroenterology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China, [31]Department of Thoracic Surgery and Medical Research Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830054, China, [32]Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China, [33]Department of Nephrology, Huaihe Hospital, Henan University, Kaifeng, Henan 475000, China, [34]Department of Oncology, Xinyang Central Hospital, Xinyang, Henan 464000, China, [35]Department of Gastroenterology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China, 临床科室消化内科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[36]Department of Surgery, The Red Cross Hospital of Huojia, Xinxiang, Henan 453800, China, [37]Department of Oncology, Puyang City Oil Field Hospital, Puyang, Henan 457000, China, [38]Department of Internal Mongolia Medicine, The Affiliated Hospital, Inner Mongolia Medical College, Huhhot, Inner Mongolia 010050, China, [39]Department of Biotechnology, Ningxia Medical University, Yinchuan, Ningxia 750004, China, [40]Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Xi’an, Shaanxi 710061, China, [41]Department of Thoracic and Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China, 四川大学华西医院[42]Department of Oncologic Pathology and Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, Guangdong 515041, China, [43]Department of Oncology and Pathology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, China, [44]Department of Biostatistics, Neihuang Public Health Bureau, Anyang, Henan 4563000, China, [45]Department of Gastroenterology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan 650011, China, [46]Department of Thoracic Surgery, Chinese Medicine Hospital of Linzhou, Linzhou, Henan 456550, China, [47]Department of Oncologic Pathology, Langzhongshi People’s Hospital, Langzhong, Sichuan 637400, China, [48]State Key Laboratory of Genetic Resource and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China, [49]Department of Thoracic Surgery, Linzhou People’s Hospital, Linzhou, Henan 456550, China, [50]Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, [51]College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China [52]MCW Cancer Center, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P 5 10(8), and the strongest signal was rs13016963, with a combined odds ratio (95 confidence interval) of 1.29 (1.191.40) and P 7.63 10(10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
基金:
Xinxiang Medical University [2009-5]; National Natural Science Foundations of ChinaNational Natural Science Foundation of China (NSFC) [30670956, 30971133]; 863 HighTech Key ProjectsNational High Technology Research and Development Program of China [2006AA02A403, 2007AA02Z161]; China Key Program on Basic Research [2007CB516812]; Science and Technology DepartmentScience and Technology Development Fund (STDF)United States Agency for International Development (USAID)US-Egypt Science and Technology Joint Fund [2009-8]; Health Department [2009-10]; Education Department of Henan Province [2008-7]; Anhui Provincial Special Scientific Program [2007-7]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA82729, R37 CA70837, NO2-CP-11010, R01 CA55069, R35 CA53890, R01 CA80205, R01 CA144034, NO2-SC-66211, NO1-SC-91030, HHSN261200477001C]; Vanderbilt University; Shanxi Cancer Hospital; Institute, Taiyuan, Shanxi, China; Cancer Institute of the Chinese Academy of Medical Sciences, Beijing, China; NIH, National Cancer Institute, Division of Cancer Epidemiology and GeneticsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; DIVISION OF CLINICAL SCIENCES - NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [N01SC091030] Funding Source: NIH RePORTER; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIACP000112, R01CA082729, R35CA053890, R01CA055069, U54CA163069, R01CA144034, R01CA080205, R03CA070837, R37CA070867, ZIACP010201] Funding Source: NIH RePORTER
第一作者机构:[1]Division of Cancer Epidemiology and Genetics
通讯作者:
通讯机构:[4]Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan 453003, China, [5]Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital
推荐引用方式(GB/T 7714):
Christian C. Abnet,Zhaoming Wang,Xin Song,et al.Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies[J].HUMAN MOLECULAR GENETICS.2012,21(9):2132-2141.doi:10.1093/hmg/dds029.
APA:
Christian C. Abnet,Zhaoming Wang,Xin Song,Nan Hu,Fu-You Zhou...&Li-Dong Wang.(2012).Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.HUMAN MOLECULAR GENETICS,21,(9)
MLA:
Christian C. Abnet,et al."Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies".HUMAN MOLECULAR GENETICS 21..9(2012):2132-2141