Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies

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	Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies
	Abnet CC 1; Wang ZM 3; Song X 4,5; Hu N 7; Zhou FY 7; Freedman ND 8; Li XM 8; Kong QP 9
刊名	HUMAN MOLECULAR GENETICS
	2012
卷号	21 期号:9 页码:2132-2141
通讯作者	abnetc@mail.nih.gov
英文摘要	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.
收录类别	SCI
资助信息	This work was supported by the Xinxiang Medical University Key Scientific Program (2009-5), the National Natural Science Foundations of China (30670956, 30971133), 863 HighTech Key Projects (2006AA02A403, 2007AA02Z161), China Key Program on Basic Research (2007CB516812), Special Scien- tific Programs from Science and Technology Department (2009-8), Health Department (2009-10) and Education Depart- ment (2008-7) of Henan Province and the Anhui Provincial Special Scientific Program (2007-7). The Shanghai Men’s Health Study (SMHS) was supported by the National Cancer Institute extramural research grant (R01 CA82729). The Shanghai Women’s Health Study (SWHS) was supported by the National Cancer Institute extramural research grant (R37 CA70837) and, partially for biological sample collection, Na- tional Cancer Institute Intramural Research Program contract NO2-CP-11010 with Vanderbilt University. The Singapore Chinese Health Study (SCHS) was supported by the National Cancer Institute extramural research grants (R01 CA55069, R35 CA53890, R01 CA80205 and R01 CA144034). The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by the National Cancer Institute Intramural Re- search Program contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi, China. The Nutrition Intervention Trials (NIT) were supported by Nation- al Cancer Institute Intramural Research Program contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences, Beijing, China. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics.
语种	英语
WOS记录号	WOS:000302302800018
公开日期	2012-04-20
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/6920]
专题	昆明动物研究所_分子人类学昆明动物研究所_遗传资源与进化国家重点实验室
作者单位	1.NCI, Nutr Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA 2.NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA 3.SAIC Frederick, Core Genotyping Facil, NCI Frederick, Frederick, MD USA 4.Xinxiang Med Univ, Canc Res Ctr, Xinxiang 453003, Henan, Peoples R China 5.Zhengzhou Univ, Affiliated Hosp 1, Henan Key Lab Esophageal Canc Res, Zhengzhou 450052, Henan, Peoples R China 6.Zhengzhou Univ, Affiliated Hosp 2, Dept Basic Oncol & Pathol, Zhengzhou 450052, Henan, Peoples R China 7.Anyang Tumor Hosp, Dept Thorac Surg & Tumor Prevent Treatment, Anyang 455000, Henan, Peoples R China 8.Cixian Hosp, Dept Pathol & Thorac Surg, Ctr Hlth Screening & Endoscopy, Cixian 056500, Hebei, Peoples R China 9.Chinese Acad Sci, State Key Lab Genet Resource & Evolut, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Abnet CC,Wang ZM,Song X,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.
APA	Abnet CC.,Wang ZM.,Song X.,Hu N.,Zhou FY.,...&Kong QP.(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),2132-2141.
MLA	Abnet CC,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.