Genome-wide association studies: inherent limitations and future challenges

doi:10.1007/s11684-012-0225-3

Front Med

2012, Vol. 6

Issue (4) : 444-450 https://doi.org/10.1007/s11684-012-0225-3

COMMENTARY

Genome-wide association studies: inherent limitations and future challenges

Yan Du, Jiaxin Xie, Wenjun Chang, Yifang Han, Guangwen Cao(

)

Department of Epidemiology, Second Military Medical University, Shanghai 200433, China

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Abstract

Genome-wide association studies (GWAS) have achieved great success in identifying genetic variants related to complex human diseases such as cancer and have provided valuable insights into their genetic architecture. Recently, GWAS is quite the fashion in China. However, there are issues related to its nature. Enormous work needs to be done in the post-GWAS era. Deep sequencing followed by functional studies will be needed to elucidate the underpinning biological mechanisms and further translate GWAS findings into medical practice. Along with pharmacogenomics, the success of GWAS in identifying genetic risk factors and genetic differences in drug response has been gradually enabling personalized medicine. In this article, we used hepatocellular carcinoma (HCC) as an example to demonstrate some of the inherent limitations and summarized future challenges of GWAS.

Keywords genome-wide association studies (GWAS) genetic variant cancer limitation challenge

Corresponding Author(s): Cao Guangwen,Email:gcao@smmu.edu.cn

Issue Date: 05 December 2012

Cite this article:

Yan Du,Jiaxin Xie,Wenjun Chang, et al. Genome-wide association studies: inherent limitations and future challenges[J]. Front Med, 2012, 6(4): 444-450.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0225-3
https://academic.hep.com.cn/fmd/EN/Y2012/V6/I4/444

Author [year] [reference]	Cancer type	Sample size (cases vs. controls)	Locus/loci	Main findings (OR, 95%CIs or P)
Zhang H [2010] [2]	Hepatocellular carcinoma (HCC)	Stage 1: 355 chronic HBV carriers w/ HCC vs. 360 chronic HBV carriers w/o HCCConfirmation Stage: 1 962 w/ HCC vs. 1 430 controls and 159 family trios	KIF1B(1p36.22): rs17401966 (intronic)	Joint OR= 0.61, P = 1.7 × 10^-18
Chan KY [2011] [3]	Hepatocellular carcinoma (HCC)	Stage 1: 95 HBV-infected HCC vs. 97 HBV-infected w/o HCCValidation Stage: 500 vs. 728	8p12: rs12682266, rs7821974, rs2275959, rs1573266	OR(combined) = 1.31–1.39; P(combined) = 2.71 × 10^-5 to 5.19 × 10^-4; PAR(combined) = 26%-31%
Abnet CC [2010] [4]	Gastric adenocarcinoma & esophageal squamous cell carcinoma (ESCC)	2 240 gastric cancer cases,2 115 ESCC cases and 3 302 controls	PLCE1(10q23): rs2274223 (non-synonymous)	Gastric cancer (per-allele OR= 1.31, P = 8.40 × 10^-9)ESCC (OR= 1.34, P = 3.85 × 10^-9)
Wang LD [2010] [5]	Esophageal squamous cell carcinoma (ESCC) &gastric cardia adenocarcinoma (GCA)	ESCCStage 1: 1 077 vs. 1 733;Stage 2: 7 673 vs. 11 013 (Han) & 303 vs. 537 (Uygur-Kazakh)GCA2 766 vs. 11 013	PLCE1 (10q23);C20orf54 (20p13).	P(Han combined for ESCC) = 7.46 × 10^-56, OR= 1.43; P(Uygur-Kazakh for ESCC) = 5.70 × 10^-4, OR= 1.53;P(Han combined for ESCC) = 1.21 × 10^-11, OR= 0.86; P(Uygur-Kazakh for ESCC) = 7.88 × 10^-3, OR= 0.66.P(Han for GCA) = 1.74 × 10^-39, OR= 1.55P(Han for GCA) = 3.02 × 10^-3, OR= 0.91
Wu C [2011] [6]	Esophageal squamous-cell carcinoma (ESCC)	Stage 1: 2 031 vs. 2 044;Stage 2: 6 276 vs. 6 165	5q11, 6p21, 10q23, 12q24 and 21q22	P = 7.48 × 10^-12 to P = 2.44 × 10^-31
Shi Y [2011] [7]	Non-cardia gastric cancer	Stage 1: 1 006 vs. 2 273;Stage 2: 3 288 vs. 3 609	5p13.1 / PTGER4 & PRKAA1: rs13361707;3q13.31 / ZBTB20: rs9841504	OR= 1.41, P = 7.6 × 10^-29OR= 0.76, P = 1.7 × 10^-9
Bei JX [2010] [8]	Nasopharyngeal carcinoma (NPC)	Stage 1: 1 583 vs. 1 894;Stage 2: 3 507 vs. 3 063;279 trios	TNFRSF19(13q12): rs9510787;MDS1-EVI1(3q26): rs6774494;CDKN2A-CDKN2B gene cluster (9p21): rs1412829;HLA: rs2860580, rs2894207, rs28421666	OR= 1.20, P(combined) = 1.53 × 10^-9OR= 0.84, P(combined) = 1.34 × 10^-8OR= 0.78, P(combined) = 4.84 × 10^-7OR= 0.58, P(combined) = 4.88 × 10^-67OR= 0.61, P(combined) = 3.42 × 10^-33OR= 0.67, P(combined) = 2.49 × 10^-18
Hu Z [2011] [9]	Lung cancer	Stage 1: 2 331 vs. 3 077;Stage 2: 6 313 vs. 6 409	TP63(3q28): rs4488809;TERT-CLPTM1L(5p15.33): rs465498, rs2736100;MIPEP-TNFRSF19(13q12.12): rs753955;MTMR3-HORMAD2-LIF(22q12.2): rs17728461, rs36600	P = 7.2 × 10^-26;P = 1.2 × 10^-20, P = 1.0 × 10^-27;P = 1.5 × 10^-12;P = 1.1 × 10^-11,P = 6.2 × 10^-13
Wu C [2012] [10]	Pancreatic cancer	Stage 1: 981 vs. 1 991;Stage 2: 2 603 vs. 2 877	21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11	P = 2.24 × 10^-13 to P = 4.18 × 10^-10
Long J [2012] [1]	Endometrial cancer	Stage 1: 832 vs. 2 682;Stage 2: 1 265 vs. 5 190;Stage 3a: 459 vs. 558;Stage 3b: 5 936 vs. 8 166	near CAPN9(1q42.2): rs1202524	OR= 1.09 (95% CI: 1.03-1.16) for the A/G genotype,OR= 1.17 (95% CI: 1.05-1.30) for the G/G genotype,P(combined) = 1.6 × 10^-4

Tab.1 Selected cancer GWAS conducted in Chinese population

1	Long J, Zheng W, Xiang YB, Lose FA, Thompson DJ, Tomlinson I, Yu H, Wentzensen N, Lambrechts D, D?rk T, Dubrowinskaja N, Goodman MT, Salvesen HB, Fasching PA, Scott RJ, Delahanty R, Zheng Y, O’Mara TA, Healey CS, Hodgson SV, Risch H, Yang HP, Amant F, Turmanov N, Schwake A, Lurie G, Trovik J, Beckmann MW, Ashton KA, Ji BT, Bao PP, Howarth K, Lu L, Lissowska J, Coenegrachts L, Kaidarova D, Dürst M, Thompson PJ, Krakstad C, Ekici AB, Otton G, Shi J, Zhang B, Gorman M, Brinton LA, Coosemans A, Matsuno RK, Halle MK, Hein A, Proietto A, Cai H, Lu W, Dunning A, Easton DF, Gao YT, Cai Q, Spurdle AB, Shu XO. Genome-wide association study identifies a possible susceptibility locus for endometrial cancer. Cancer Epidemiol Biomarkers Prev 2012; 21(6): 980-987 doi: 10.1158/1055-9965.EPI-11-1160 pmid:22426144
2	Zhang H, Zhai Y, Hu Z, Wu C, Qian J, Jia W, Ma F, Huang W, Yu L, Yue W, Wang Z, Li P, Zhang Y, Liang R, Wei Z, Cui Y, Xie W, Cai M, Yu X, Yuan Y, Xia X, Zhang X, Yang H, Qiu W, Yang J, Gong F, Chen M, Shen H, Lin D, Zeng YX, He F, Zhou G. Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat Genet 2010; 42(9): 755-758 doi: 10.1038/ng.638 pmid:20676096
3	Chan KY, Wong CM, Kwan JS, Lee JM, Cheung KW, Yuen MF, Lai CL, Poon RT, Sham PC, Ng IO. Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection. PLoS ONE 2011; 6(12): e28798 doi: 10.1371/journal.pone.0028798 pmid:22174901
4	Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, Yuan JM, Zheng W, Dawsey SM, Dong LM, Lee MP, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Wang C, Wheeler W, Gail MH, Yeager M, Yuenger J, Hutchinson A, Jacobs KB, Giffen CA, Burdett L, Fraumeni JF Jr, Tucker MA, Chow WH, Goldstein AM, Chanock SJ, Taylor PR. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet 2010; 42(9): 764-767 doi: 10.1038/ng.649 pmid:20729852
5	Wang LD, Zhou FY, Li XM, Sun LD, Song X, Jin Y, Li JM, Kong GQ, Qi H, Cui J, Zhang LQ, Yang JZ, Li JL, Li XC, Ren JL, Liu ZC, Gao WJ, Yuan L, Wei W, Zhang YR, Wang WP, Sheyhidin I, Li F, Chen BP, Ren SW, Liu B, Li D, Ku JW, Fan ZM, Zhou SL, Guo ZG, Zhao XK, Liu N, Ai YH, Shen FF, Cui WY, Song S, Guo T, Huang J, Yuan C, Huang J, Wu Y, Yue WB, Feng CW, Li HL, Wang Y, Tian JY, Lu Y, Yuan Y, Zhu WL, Liu M, Fu WJ, Yang X, Wang HJ, Han SL, Chen J, Han M, Wang HY, Zhang P, Li XM, Dong JC, Xing GL, Wang R, Guo M, Chang ZW, Liu HL, Guo L, Yuan ZQ, Liu H, Lu Q, Yang LQ, Zhu FG, Yang XF, Feng XS, Wang Z, Li Y, Gao SG, Qige Q, Bai LT, Yang WJ, Lei GY, Shen ZY, Chen LQ, Li EM, Xu LY, Wu ZY, Cao WK, Wang JP, Bao ZQ, Chen JL, Ding GC, Zhuang X, Zhou YF, Zheng HF, Zhang Z, Zuo XB, Dong ZM, Fan DM, He X, Wang J, Zhou Q, Zhang QX, Jiao XY, Lian SY, Ji AF, Lu XM, Wang JS, Chang FB, Lu CD, Chen ZG, Miao JJ, Fan ZL, Lin RB, Liu TJ, Wei JC, Kong QP, Lan Y, Fan YJ, Gao FS, Wang TY, Xie D, Chen SQ, Yang WC, Hong JY, Wang L, Qiu SL, Cai ZM, Zhang XJ. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet 2010; 42(9): 759-763 doi: 10.1038/ng.648 pmid:20729853
6	Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, Liu Z, Zhan Q, Liu Y, Yu D, Zhai K, Chang J, Qiao Y, Jin G, Liu Z, Shen Y, Guo C, Fu J, Miao X, Tan W, Shen H, Ke Y, Zeng Y, Wu T, Lin D. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet 2011; 43(7): 679-684 doi: 10.1038/ng.849 pmid:21642993
7	Shi Y, Hu Z, Wu C, Dai J, Li H, Dong J, Wang M, Miao X, Zhou Y, Lu F, Zhang H, Hu L, Jiang Y, Li Z, Chu M, Ma H, Chen J, Jin G, Tan W, Wu T, Zhang Z, Lin D, Shen H. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet 2011; 43(12): 1215-1218 doi: 10.1038/ng.978 pmid:22037551
8	Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, Feng QS, Low HQ, Zhang H, He F, Tai ES, Kang T, Liu ET, Liu J, Zeng YX. A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet 2010; 42(7): 599-603 doi: 10.1038/ng.601 pmid:20512145
9	Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H. A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 2011; 43(8): 792-796 doi: 10.1038/ng.875 pmid:21725308
10	Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, Yang X, Cao G, Hu Z, Zhou Y, Zuo C, Wang C, Zhang X, Zhou Y, Yu X, Dai W, Li Z, Shen H, Liu L, Chen Y, Zhang S, Wang X, Zhai K, Chang J, Liu Y, Sun M, Cao W, Gao J, Ma Y, Zheng X, Cheung ST, Jia Y, Xu J, Tan W, Zhao P, Wu T, Wang C, Lin D. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet 2012; 44(1): 62-66 doi: 10.1038/ng.1020 pmid:22158540
11	Milestone in Anhui. Nat Genet 2011; 43(7): 613 doi: 10.1038/ng.881 pmid:21709678
12	Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 2008; 40(5): 616-622 doi: 10.1038/ng.109 pmid:18385676
13	Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Chen C, Goodman G, Field JK, Liloglou T, Xinarianos G, Cassidy A, McLaughlin J, Liu G, Narod S, Krokan HE, Skorpen F, Elvestad MB, Hveem K, Vatten L, Linseisen J, Clavel-Chapelon F, Vineis P, Bueno-de-Mesquita HB, Lund E, Martinez C, Bingham S, Rasmuson T, Hainaut P, Riboli E, Ahrens W, Benhamou S, Lagiou P, Trichopoulos D, Holcátová I, Merletti F, Kjaerheim K, Agudo A, Macfarlane G, Talamini R, Simonato L, Lowry R, Conway DI, Znaor A, Healy C, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 2008; 452(7187): 633-637 doi: 10.1038/nature06885 pmid:18385738
14	Chung CC, Chanock SJ. Current status of genome-wide association studies in cancer. Hum Genet 2011; 130(1): 59-78 doi: 10.1007/s00439-011-1030-9 pmid:21678065
15	Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM. Finding the missing heritability of complex diseases. Nature 2009; 461(7265): 747-753 doi: 10.1038/nature08494 pmid:19812666
16	Lango Allen H, Estrada K, Lettre G, Berndt S I, Weedon M N, Rivadeneira F, Willer C J, Jackson A U, Vedantam S, Raychaudhuri S, Ferreira T, Wood A R, Weyant R J, Segre A V, Speliotes E K, Wheeler E, Soranzo N, Park J H, Yang J, Gudbjartsson D, Heard-Costa N L, Randall J C, Qi L, Vernon Smith A, Magi R, Pastinen T, Liang L, Heid I M, Luan J, Thorleifsson G, Winkler T W, Goddard M E, Sin Lo K, Palmer C, Workalemahu T, Aulchenko Y S, Johansson A, Zillikens M C, Feitosa M F, Esko T, Johnson T, Ketkar S, Kraft P, Mangino M, Prokopenko I, Absher D, Albrecht E, Ernst F, Glazer N L, Hayward C, Hottenga J J, Jacobs K B, Knowles J W, Kutalik Z, Monda K L, Polasek O, Preuss M, Rayner N W, Robertson N R, Steinthorsdottir V, Tyrer J P, Voight B F, Wiklund F, Xu J, Zhao J H, Nyholt D R, Pellikka N, Perola M, Perry J R, Surakka I, Tammesoo M L, Altmaier E L, Amin N, Aspelund T, Bhangale T, Boucher G, Chasman D I, Chen C, Coin L, Cooper M N, Dixon A L, Gibson Q, Grundberg E, Hao K, Juhani Junttila M, Kaplan L M, Kettunen J, Konig I R, Kwan T, Lawrence R W, Levinson D F, Lorentzon M, McKnight B, Morris A P, Muller M, Suh Ngwa J, Purcell S, Rafelt S, Salem RM, Salvi E, Sanna S, Shi J, Sovio U, Thompson J R, Turchin M C, Vandenput L, Verlaan D J, Vitart V, White C C, Ziegler A, Almgren P, Balmforth A J, Campbell H, Citterio L, De Grandi A, Dominiczak A, Duan J, Elliott P, Elosua R, Eriksson J G, Freimer N B, Geus E J, Glorioso N, Haiqing S, Hartikainen A L, Havulinna A S, Hicks A A, Hui J, Igl W, Illig T, Jula A, Kajantie E, Kilpelainen T O, Koiranen M, Kolcic I, Koskinen S, Kovacs P, Laitinen J, Liu J, Lokki M L, Marusic A, Maschio A, Meitinger T, Mulas A, Pare G, Parker A N, Peden J F, Petersmann A, Pichler I, Pietilainen K H, Pouta A, Ridderstrale M, Rotter J I, Sambrook J G, Sanders A R, Schmidt C O, Sinisalo J, Smit J H, Stringham H M, Bragi Walters G, Widen E, Wild S H, Willemsen G, Zagato L, Zgaga L, Zitting P, Alavere H, Farrall M, McArdle W L, Nelis M, Peters M J, Ripatti S, van Meurs J B, Aben K K, Ardlie K G, Beckmann J S, Beilby J P, Bergman R N, Bergmann S, Collins F S, Cusi D, den Heijer M, Eiriksdottir G, Gejman P V, Hall A S, Hamsten A, Huikuri H V, Iribarren C, Kahonen M, Kaprio J, Kathiresan S, Kiemeney L, Kocher T, Launer L J, Lehtimaki T, Melander O, Mosley T H, Jr., Musk A W, Nieminen M S, O'Donnell C J, Ohlsson C, Oostra B, Palmer L J, Raitakari O, Ridker P M, Rioux J D, Rissanen A, Rivolta C, Schunkert H, Shuldiner A R, Siscovick D S, Stumvoll M, Tonjes A, Tuomilehto J, van Ommen G J, Viikari J, Heath A C, Martin N G, Montgomery G W, Province M A, Kayser M, Arnold A M, Atwood L D, Boerwinkle E, Chanock S J, Deloukas P, Gieger C, Gronberg H, Hall P, Hattersley A T, Hengstenberg C, Hoffman W, Lathrop G M, Salomaa V, Schreiber S, Uda M, Waterworth D, Wright A F, Assimes T L, Barroso I, Hofman A, Mohlke K L, Boomsma D I, Caulfield M J, Cupples L A, Erdmann J, Fox C S, Gudnason V, Gyllensten U, Harris T B, Hayes R B, Jarvelin M R, Mooser V, Munroe P B, Ouwehand W H, Penninx B W, Pramstaller P P, Quertermous T, Rudan I, Samani N J, Spector T D, Volzke H, Watkins H, Wilson J F, Groop L C, Haritunians T, Hu F B, Kaplan R C, Metspalu A, North K E, Schlessinger D, Wareham N J, Hunter D J, O'Connell J R, Strachan D P, Wichmann H E, Borecki I B, van Duijn C M, Schadt E E, Thorsteinsdottir U, Peltonen L, Uitterlinden A G, Visscher P M, Chatterjee N, Loos R J, Boehnke M, McCarthy M I, Ingelsson E, Lindgren C M, Abecasis G R, Stefansson K, Frayling T M, Hirschhorn J N. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 2010; 467(7317): 832-838 doi: 10.1038/nature09410 pmid:20881960
17	Miki D, Ochi H, Hayes CN, Aikata H, Chayama K. Hepatocellular carcinoma: towards personalized medicine. Cancer Sci 2012; 103(5): 846-850 doi: 10.1111/j.1349-7006.2012.02242.x pmid:22339805
18	Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology 2008; 48(6): 2047-2063 doi: 10.1002/hep.22580 pmid:19003900
19	Han YF, Zhao J, Ma LY, Yin JH, Chang WJ, Zhang HW, Cao GW. Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma. World J Gastroenterol 2011; 17(38): 4258-4270 doi: 10.3748/wjg.v17.i38.4258 pmid:22090781
20	Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat 2009; 16(7): 453-463 doi: 10.1111/j.1365-2893.2009.01117.x pmid:19302335
21	Yin J, Xie J, Liu S, Zhang H, Han L, Lu W, Shen Q, Xu G, Dong H, Shen J, Zhang J, Han J, Wang L, Liu Y, Wang F, Zhao J, Zhang Q, Ni W, Wang H, Cao G. Association between the various mutations in viral core promoter region to different stages of hepatitis B, ranging of asymptomatic carrier state to hepatocellular carcinoma. Am J Gastroenterol 2011; 106(1): 81-92 doi: 10.1038/ajg.2010.399 pmid:20959817
22	Xie JX, Zhao J, Yin JH, Zhang Q, Pu R, Lu WY, Zhang HW, Wang HY, Cao GW. Association of novel mutations and haplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma. Front Med China 2010; 4(4): 419-429 doi: 10.1007/s11684-010-0160-0 pmid:21104161
23	Liu S, Zhang H, Gu C, Yin J, He Y, Xie J, Cao G. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst 2009; 101(15): 1066-1082 doi: 10.1093/jnci/djp180 pmid:19574418
24	Chen L, Hu L, Li L, Liu Y, Tu QQ, Chang YX, Yan HX, Wu MC, Wang HY. Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas. Front Med China 2010; 4(4): 399-411 doi: 10.1007/s11684-010-0170-y pmid:21107751
25	Yin J, Xie J, Zhang H, Shen Q, Han L, Lu W, Han Y, Li C, Ni W, Wang H, Cao G. Significant association of different preS mutations with hepatitis B-related cirrhosis or hepatocellular carcinoma. J Gastroenterol 2010; 45(10): 1063-1071 doi: 10.1007/s00535-010-0253-1 pmid:20419326
26	Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet 2011; 43(5): 455-458 doi: 10.1038/ng.809 pmid:21499248
27	Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, Kumada H, Toyota J, Morizono T, Tsunoda T, Kubo M, Nakamura Y, Kamatani N, Chayama K. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet 2011; 43(8): 797-800 doi: 10.1038/ng.876 pmid:21725309
28	Clifford RJ, Zhang J, Meerzaman DM, Lyu MS, Hu Y, Cultraro CM, Finney RP, Kelley JM, Efroni S, Greenblum SI, Nguyen CV, Rowe WL, Sharma S, Wu G, Yan C, Zhang H, Chung YH, Kim JA, Park NH, Song IH, Buetow KH. Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma. Hepatology 2010; 52(6): 2034-2043 doi: 10.1002/hep.23943 pmid:21105107
29	Galichon P, Hertig A, Rondeau E, Mesnard L. Warning: genome-wide association studies can be misleading. An example in hepatology. Hepatology 2011; 53(4): 1408, author reply 1408-1409 doi: 10.1002/hep.24198 pmid:21480354
30	Wang K, Li M, Hakonarson H. Analysing biological pathways in genome-wide association studies. Nat Rev Genet 2010; 11(12): 843-854 doi: 10.1038/nrg2884 pmid:21085203
31	Braun R, Buetow K. Pathways of distinction analysis: a new technique for multi-SNP analysis of GWAS data. PLoS Genet 2011; 7(6): e1002101 doi: 10.1371/journal.pgen.1002101 pmid:21695280
32	Ku CS, Loy EY, Pawitan Y, Chia KS. The pursuit of genome-wide association studies: where are we now? J Hum Genet 2010; 55(4): 195-206 doi: 10.1038/jhg.2010.19 pmid:20300123
33	Hudson T. Genome-sequencing anniversary. Genomics and clinical relevance. Science 2011; 331(6017): 547 doi: 10.1126/science.1202572 pmid:21292965

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[7]	Rui Zhou, Yuanshu Liu, Wenjun Huang, Xitong Dang. Potential functions of esophageal cancer-related gene-4 in the cardiovascular system[J]. Front. Med., 2019, 13(6): 639-645.
[8]	Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia. Altered intestinal microbiota associated with colorectal cancer[J]. Front. Med., 2019, 13(4): 461-470.
[9]	Yumeng Wang, Guiling Li. PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives[J]. Front. Med., 2019, 13(4): 438-450.
[10]	Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin. Histone variants: critical determinants in tumour heterogeneity[J]. Front. Med., 2019, 13(3): 289-297.
[11]	Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang. Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12[J]. Front. Med., 2019, 13(1): 83-93.
[12]	Synat Kang, Yanyan Li, Yifeng Bao, Yi Li. High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells[J]. Front. Med., 2019, 13(1): 69-82.
[13]	Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen. Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy[J]. Front. Med., 2019, 13(1): 57-68.
[14]	Chenfei Zhou, Jun Zhang. Immunotherapy-based combination strategies for treatment of gastrointestinal cancers: current status and future prospects[J]. Front. Med., 2019, 13(1): 12-23.
[15]	Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie. Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy[J]. Front. Med., 2018, 12(6): 667-677.

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