GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

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GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers


نویسنده	li s. ,qian j. ,yang y. ,zhao w. ,dai j. ,bei j.-x. ,foo j.n. ,mclaren p.j. ,li z. ,yang j. ,shen f. ,liu l. ,yang j. ,li s. ,pan s. ,wang y. ,li w. ,zhai x. ,zhou b. ,shi l. ,chen x. ,chu m. ,yan y. ,wang j. ,cheng s. ,shen j. ,jia w. ,liu j. ,yang j. ,wen z. ,li a. ,zhang y. ,zhang g. ,luo x. ,qin h. ,chen m. ,wang h. ,jin l. ,lin d. ,shen h. ,he l. ,de bakker p.i.w. ,wang h. ,zeng y.-x. ,wu m. ,hu z. ,shi y. ,liu j. ,zhou w.
منبع	plos genetics - 2012 - دوره : 8 - شماره : 7
چکیده	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-drb10405 and 09010602,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. © 2012 li et al.

آدرس	department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, state key laboratory of genetic engineering,center for fudan-vari genetic epidemiology and moe key laboratory of contemporary anthropology,school of life sciences,fudan university,shanghai, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, human genetics,genome institute of singapore,a star,singapore, Singapore, moe key laboratory of modern toxicology,jiangsu key laboratory of cancer biomarkers,prevention,and treatment,state key laboratory of reproductive medicine,nanjing medical university,nanjing, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, division of genetics,brigham and women's hospital,harvard medical school boston and broad institute of harvard and mit,cambridge,ma, United States, division of genetics,brigham and women's hospital,harvard medical school boston and broad institute of harvard and mit,cambridge,ma, United States, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai, China, state key laboratory of genetic engineering,center for fudan-vari genetic epidemiology and moe key laboratory of contemporary anthropology,school of life sciences,fudan university,shanghai, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, department of hepatobiliary surgery,nantong tumor hospital,nantong, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, moe key laboratory of modern toxicology,jiangsu key laboratory of cancer biomarkers,prevention,and treatment,state key laboratory of reproductive medicine,nanjing medical university,nanjing, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai, China, department of infection diseases,jiangsu province center for disease prevention and control,nanjing, China, the third people's municipal hospital of shenzhen,shenzhen, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, the third people's municipal hospital of shenzhen,shenzhen, China, moe key laboratory of modern toxicology,jiangsu key laboratory of cancer biomarkers,prevention,and treatment,state key laboratory of reproductive medicine,nanjing medical university,nanjing, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, department of hepatobiliary surgery,nantong tumor hospital,nantong, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, the third people's municipal hospital of shenzhen,shenzhen, China, no. 458 hospital of chinese people's liberation army,guangzhou, China, the eighth municipal people's hospital of guangzhou,guangzhou, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, department of infection diseases,jiangsu province center for disease prevention and control,nanjing, China, state key laboratory of genetic engineering,center for fudan-vari genetic epidemiology and moe key laboratory of contemporary anthropology,school of life sciences,fudan university,shanghai, China, 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, China, moe key laboratory of modern toxicology,jiangsu key laboratory of cancer biomarkers,prevention,and treatment,state key laboratory of reproductive medicine,nanjing medical university,nanjing, China, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai,china,institutes for nutritional sciences,shanghai institute of biological sciences,chinese academy of sciences,shanghai,china,institutes of biomedical sciences,fudan university,shanghai, China, division of genetics,brigham and women's hospital,harvard medical school boston and broad institute of harvard and mit,cambridge,ma, United States, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, department of hepatobiliary oncology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou, China, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China, moe key laboratory of modern toxicology,jiangsu key laboratory of cancer biomarkers,prevention,and treatment,state key laboratory of reproductive medicine,nanjing medical university,nanjing, China, bio-x institutes,key lab. for the genetics of developmental and neuropsychiatric disorders (ministry of education),shanghai jiao tong university,shanghai, China, human genetics,genome institute of singapore,a star,singapore, Singapore, eastern hepatobiliary surgery hospital,second military medical university,shanghai, China



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