Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma

被引：262

作者：

Jiang, De-Ke ^{[1
]}

Sun, Jielin ^{[2
]}

Cao, Guangwen ^{[3
]}

Liu, Yao ^{[4
,5
,6
]}

Lin, Dongxin ^{[7
,8
]}

Gao, Yu-Zhen ^{[9
]}

Ren, Wei-Hua ^{[1
,10
]}

Long, Xi-Dai ^{[11
]}

Zhang, Hongxing ^{[12
]}

Ma, Xiao-Pin ^{[1
]}

Wang, Zhong ^{[2
]}

Jiang, Wei ^{[1
]}

Chen, Tao-Yang ^{[13
]}

Gao, Yong ^{[14
,15
,16
]}

Sun, Liang-Dan ^{[17
,18
,19
]}

Long, Ji-Rong ^{[20
]}

Huang, Hui-Xing ^{[1
]}

Wang, Dan ^{[1
]}

Yu, Hongjie ^{[16
]}

Zhang, Pengyin ^{[16
]}

Tang, Li-Sha ^{[1
]}

Peng, Bo ^{[1
]}

Cai, Hao ^{[1
]}

Liu, Ting-Ting ^{[1
]}

Zhou, Ping ^{[1
]}

Liu, Fang ^{[16
]}

Lin, Xiaoling ^{[16
]}

Tao, Sha ^{[2
]}

Wan, Bo ^{[1
]}

Sai-Yin, He-Xi Ge ^{[1
]}

Qin, Lun-Xiu ^{[21
,22
]}

Yin, Jianhua ^{[3
]}

Liu, Li ^{[23
]}

Wu, Chen ^{[7
,8
]}

Pei, Yan ^{[10
]}

Zhou, Yuan-Feng ^{[11
]}

Zhai, Yun ^{[12
]}

Lu, Pei-Xin ^{[13
]}

Tan, Aihua ^{[14
,15
]}

Zuo, Xian-Bo ^{[17
,18
,19
]}

Fan, Jia ^{[21
,22
]}

Chang, Jiang ^{[7
,8
]}

Gu, Xiaoli ^{[12
]}

Wang, Neng-Jin ^{[13
]}

Li, Yang ^{[17
,18
,19
]}

Liu, Yin-Kun ^{[21
,22
]}

Zhai, Kan ^{[7
,8
]}

Zhang, Hongwei ^{[3
]}

Hu, Zhibin ^{[4
,5
,6
]}

Liu, Jun ^{[1
,24
]}

机构：

[1] Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China

[2] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA

[3] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China

[4] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Minist Educ, Nanjing, Peoples R China

[5] Nanjing Med Univ, Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China

[6] Nanjing Med Univ, State Key Lab Reprod Med, Sch Publ Hlth, Nanjing, Peoples R China

[7] Chinese Acad Med Sci, Dept Etiol & Carcinogenesis, Canc Inst & Hosp, Beijing 100730, Peoples R China

[8] Peking Union Med Coll, Beijing 100021, Peoples R China

[9] Soochow Univ, Dept Forens Med, Coll Med, Suzhou, Peoples R China

[10] Henan Univ Sci & Technol, Dept Surg, Affiliated Hosp 1, Luoyang, Peoples R China

[11] Youjiang Med Coll Nationalities, Dept Pathol, Baise, Peoples R China

[12] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China

[13] Qidong Liver Canc Inst, Qidong, Peoples R China

[14] Guangxi Med Univ, Inst Urol & Nephrol, Affiliated Hosp 1, Nanning, Peoples R China

[15] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning, Peoples R China

[16] Fudan Univ, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China

[17] Anhui Med Univ, Inst Dermatol, Hefei, Peoples R China

[18] Anhui Med Univ, Dept Dermatol, Hosp 1, Hefei, Peoples R China

[19] Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei, Peoples R China

[20] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37212 USA

[21] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China

[22] Fudan Univ, Dept Liver Surg, Zhongshan Hosp, Shanghai 200433, Peoples R China

[23] Nantong Tumor Hosp, Dept Hepatobiliary Surg, Nantong, Peoples R China

[24] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[25] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA

[26] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA

[27] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA

[28] Shanghai Canc Inst, Shanghai, Peoples R China

[29] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China

[30] Fudan Univ, Fudan Inst Urol, Huashan Hosp, Shanghai 200433, Peoples R China

[31] NIMH, Unit Stat Genom, Div Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA

[32] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

来源：

NATURE GENETICS | 2013年 / 45卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCUS; INTERFERON-GAMMA; VIRAL-INFECTION; POPULATION; ALLELES; CHINESE;

D O I：

10.1038/ng.2483

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P-meta = 2.48 x 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P-meta = 2.72 x 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P-trend = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 x 10(-14)).

引用

页码：72 / U105

页数：6

共 45 条

[1] Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB As Novel Risk Loci for Systemic Sclerosis [J].

Allanore, Yannick ;

Saad, Mohamad ;

Dieude, Philippe ;

Avouac, Jerome ;

Distler, Jorg H. W. ;

Amouyel, Philippe ;

Matucci-Cerinic, Marco ;

Riemekasten, Gabriella ;

Airo, Paolo ;

Melchers, Inga ;

Hachulla, Eric ;

Cusi, Daniele ;

Wichmann, H. -Erich ;

Wichmann, Erich ;

Wipff, Julien ;

Lambert, Jean-Charles ;

Hunzelmann, Nicolas ;

Tiev, Kiet ;

Caramaschi, Paola ;

Diot, Elisabeth ;

Kowal-Bielecka, Otylia ;

Valentini, Gabriele ;

Mouthon, Luc ;

Czirjak, Laszlo ;

Damjanov, Nemanja ;

Salvi, Erika ;

Conti, Costanza ;

Mueller, Martina ;

Mueller-Ladner, Ulf ;

Riccieri, Valeria ;

Ruiz, Barbara ;

Cracowski, Jean-Luc ;

Letenneur, Luc ;

Dupuy, Anne Marie ;

Meyer, Oliver ;

Kahan, Andre ;

Munnich, Arnold ;

Boileau, Catherine ;

Martinez, Maria .

PLOS GENETICS, 2011, 7 (07)

[2] Power play: Scoring our goals for liver cancer with better GWAS study design [J].

Budhu, Anuradha ;

Wang, Xin Wei .

JOURNAL OF HEPATOLOGY, 2011, 54 (04) :823-824

[3]

Casper Markus, 2011, Hepatology, V53, P1390, DOI 10.1002/hep.24241

[4] Liver cancer epidemic in China: Past, present and future [J].

Chen, Jian Guo ;

Zhang, Si Wei .

SEMINARS IN CANCER BIOLOGY, 2011, 21 (01) :59-69

[5] Improved multiplex-PCR to identify hepatitis B virus genotypes A-F and subgenotypes B1, B2, C1 and C2 [J].

Chen, Jinsong ;

Yin, Jianhua ;

Tan, Xiaojie ;

Zhang, Haiqin ;

Zhang, Hongwei ;

Chen, Beichuan ;

Chang, Wenjun ;

Schaefer, Stephan ;

Cao, Guangwen .

JOURNAL OF CLINICAL VIROLOGY, 2007, 38 (03) :238-243

[6] Regulation of major histocompatibility complex class II genes [J].

Choi, Nancy M. ;

Majumder, Parimal ;

Boss, Jeremy M. .

CURRENT OPINION IN IMMUNOLOGY, 2011, 23 (01) :81-87

[7] Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti-dsDNA Autoantibody Production [J].

Chung, Sharon A. ;

Taylor, Kimberly E. ;

Graham, Robert R. ;

Nititham, Joanne ;

Lee, Annette T. ;

Ortmann, Ward A. ;

Jacob, Chaim O. ;

Alarcon-Riquelme, Marta E. ;

Tsao, Betty P. ;

Harley, John B. ;

Gaffney, Patrick M. ;

Moser, Kathy L. ;

Petri, Michelle ;

Demirci, F. Yesim ;

Kamboh, M. Ilyas ;

Manzi, Susan ;

Gregersen, Peter K. ;

Langefeld, Carl D. ;

Behrens, Timothy W. ;

Criswell, Lindsey A. .

PLOS GENETICS, 2011, 7 (03)

[8] Interferons, immunity and cancer immunoediting [J].

Dunn, Gavin P. ;

Koebel, Catherine M. ;

Schreiber, Robert D. .

NATURE REVIEWS IMMUNOLOGY, 2006, 6 (11) :836-848

[9] Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].

El-Serag, Hashem B. ;

Rudolph, Lenhard .

GASTROENTEROLOGY, 2007, 132 (07) :2557-2576

[10] An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1α 3' untranslated region confers risk for hepatocellular carcinoma [J].

Gao, Yuzhen ;

He, Yan ;

Ding, Jun ;

Wu, Kang ;

Hu, Bo ;

Liu, Yang ;

Wu, Yan ;

Guo, Bingnan ;

Shen, Yueping ;

Landi, Debora ;

Landi, Stefano ;

Zhou, Yifeng ;

Liu, Haiyan .

CARCINOGENESIS, 2009, 30 (12) :2064-2069

← 1 2 3 4 5 →