Genome-wide association study of cervical cancer suggests a role for ARRDC3 gene in human papillomavirus infection

被引：35

作者：

Takeuchi, Fumihiko ^{[1
]}

Kukimoto, Iwao ^{[2
]}

Li, Zhiqiang ^{[3
,4
,5
,6
,7
]}

Li, Shuang ^{[8
]}

Li, Ni ^{[9
,10
]}

Hu, Zhibin ^{[11
,12
]}

Takahashi, Atsushi ^{[13
,14
]}

Inoue, Shusaku ^{[15
]}

Yokoi, Sana ^{[16
,17
]}

Chen, Jianhua ^{[5
,6
,18
]}

Hang, Dong ^{[11
]}

Kuroda, Makoto ^{[19
]}

Matsuda, Fumihiko ^{[20
]}

Mizuno, Mika ^{[21
]}

Mori, Seiichiro ^{[2
]}

Wu, Peng ^{[8
]}

Tanaka, Naotake ^{[22
]}

Matsuo, Keitaro ^{[15
,23
]}

Kamatani, Yoichiro ^{[13
,20
]}

Kubo, Michiaki ^{[24
]}

Ma, Ding ^{[8
]}

Shi, Yongyong ^{[3
,4
,5
,6
,7
,18
]}

机构：

[1] Natl Ctr Global Hlth & Med, Res Inst, Tokyo 1628655, Japan

[2] Natl Inst Infect Dis, Pathogen Genom Ctr, Musashimurayama, Tokyo, Japan

[3] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China

[4] Qingdao Univ, Biomed Sci Inst, Qingdao Branch, SJTU Bio X Inst, Qingdao, Peoples R China

[5] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Brain Sci, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst,Minist Educ, Shanghai, Peoples R China

[6] Shanghai Jiao Tong Univ, Inst Social Cognit & Behav Sci, Shanghai, Peoples R China

[7] Shanghai Jiao Tong Univ, Inst Neuropsychiat Sci & Syst Biol Med, Shanghai, Peoples R China

[8] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Hubei, Peoples R China

[9] Chinese Acad Med Sci, Canc Hosp, Natl Canc Ctr, Program Off Canc Screening Urban China, Beijing, Peoples R China

[10] Peking Union Med Coll, Beijing, Peoples R China

[11] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Sch Publ Hlth,Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China

[12] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[13] RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[14] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Genom Med, Osaka, Japan

[15] Aichi Canc Ctr, Res Inst, Div Mol & Clin Epidemiol, Nagoya, Aichi, Japan

[16] Chiba Canc Ctr, Res Inst, Canc Genome Ctr, Chiba, Japan

[17] Chiba Canc Ctr, Div Genet Diagnost, Chiba, Japan

[18] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China

[19] Natl Inst Infect Dis, Pathogen Genom Ctr, Shinjuku Ku, Tokyo, Japan

[20] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[21] Aichi Canc Ctr Hosp, Dept Gynecol Oncol, Nagoya, Aichi, Japan

[22] Chiba Canc Ctr, Div Gynecol, Chiba, Japan

[23] Nagoya Univ, Grad Sch Med, Dept Epidemiol, Nagoya, Aichi, Japan

[24] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

来源：

HUMAN MOLECULAR GENETICS | 2019年 / 28卷 / 02期

基金：

国家重点研发计划; 日本学术振兴会;

关键词：

SUSCEPTIBILITY LOCI; POLISH POPULATION; VARIANT; BINDING; BASAL; RISK; UBIQUITINATION; ARCHITECTURE; POLYMORPHISM; ANNOTATION;

D O I：

10.1093/hmg/ddy390

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The development of cervical cancer is initiated by human papillomavirus (HPV) infection and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage and 1461 cases and 3295 controls in the follow-up stage. We identified novel-significant associations at 5q14 with the lead single nucleotide polymorphism (SNP) rs59661306 (P = 2.4 x 10(-11)) and at 7p11 with the lead SNP rs7457728 (P = 1.2 x 10(-8)). In 5q14, the chromatin region of the GWAS-significant SNPs was found to be in contact with the promoter of the ARRDC3 (arrestin domain-containing 3) gene. In our functional studies, ARRDC3 knockdown in HeLa cells caused significant reductions in both cell growth and susceptibility to HPV16 pseudovirion infection, suggesting that ARRDC3 is involved in the infectious entry of HPV into the cell. Our study advances the understanding of host genes that are responsible for cervical cancer susceptibility and guides future research on HPV infection and cancer development.

引用

页码：341 / 348

页数：8

共 61 条

[1] Integrated profiling of basal and luminal breast cancers [J].

Adelaide, Jose ;

Finetti, Pascal ;

Bekhouche, Ismahane ;

Repellini, Laetitia ;

Geneix, Jeannine ;

Sircoulomb, Fabrice ;

Jauffret, Emmanuelle Charafe ;

Cervera, Nathalie ;

Desplans, Jerome ;

Parzy, Daniel ;

Schoenmakers, Eric ;

Viens, Patrice ;

Jacquemier, Jocelyne ;

Birnbaum, Daniel ;

Bertucci, Francois ;

Chaffanet, Max .

CANCER RESEARCH, 2007, 67 (24) :11565-11575

[2] Genetic effects on gene expression across human tissues [J].

Aguet, Francois ;

Brown, Andrew A. ;

Castel, Stephane E. ;

Davis, Joe R. ;

He, Yuan ;

Jo, Brian ;

Mohammadi, Pejman ;

Park, Yoson ;

Parsana, Princy ;

Segre, Ayellet V. ;

Strober, Benjamin J. ;

Zappala, Zachary ;

Cummings, Beryl B. ;

Gelfand, Ellen T. ;

Hadley, Kane ;

Huang, Katherine H. ;

Lek, Monkol ;

Li, Xiao ;

Nedzel, Jared L. ;

Nguyen, Duyen Y. ;

Noble, Michael S. ;

Sullivan, Timothy J. ;

Tukiainen, Taru ;

MacArthur, Daniel G. ;

Getz, Gad ;

Management, Nih Program ;

Addington, Anjene ;

Guan, Ping ;

Koester, Susan ;

Little, A. Roger ;

Lockhart, Nicole C. ;

Moore, Helen M. ;

Rao, Abhi ;

Struewing, Jeffery P. ;

Volpi, Simona ;

Collection, Biospecimen ;

Brigham, Lori E. ;

Hasz, Richard ;

Hunter, Marcus ;

Johns, Christopher ;

Johnson, Mark ;

Kopen, Gene ;

Leinweber, William F. ;

Lonsdale, John T. ;

McDonald, Alisa ;

Mestichelli, Bernadette ;

Myer, Kevin ;

Roe, Bryan ;

Salvatore, Michael ;

Shad, Saboor .

NATURE, 2017, 550 (7675) :204-+

[3] HPV16 infection of HaCaTs is dependent on β4 integrin, and α6 integrin processing [J].

Aksoy, Pinar ;

Abban, Cynthia Y. ;

Kiyashka, Elizabeth ;

Qiang, Weitao ;

Meneses, Patricio I. .

VIROLOGY, 2014, 449 :45-52

[4]

[Anonymous], 2012, NATURE, DOI DOI 10.1038/nature11632

[5] Human Papillomavirus Genotype Distribution in Cervical Intraepithelial Neoplasia Grade 2/3 and Invasive Cervical Cancer in Japanese Women [J].

Azuma, Yukari ;

Kusumoto-Matsuo, Rika ;

Takeuchi, Fumihiko ;

Uenoyama, Asami ;

Kondo, Kazunari ;

Tsunoda, Hajime ;

Nagasaka, Kazunori ;

Kawana, Kei ;

Morisada, Tohru ;

Iwata, Takashi ;

Aoki, Daisuke ;

Kukimoto, Iwao .

JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 2014, 44 (10) :910-917

[6] Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists [J].

Badve, Sunil ;

Dabbs, David J. ;

Schnitt, Stuart J. ;

Baehner, Frederick L. ;

Decker, Thomas ;

Eusebi, Vincenzo ;

Fox, Stephen B. ;

Ichihara, Shu ;

Jacquemier, Jocelyne ;

Lakhani, Sunil R. ;

Palacios, Jose ;

Rakha, Emad A. ;

Richardson, Andrea L. ;

Schmitt, Fernando C. ;

Tan, Puay-Hoon ;

Tse, Gary M. ;

Weigelt, Britta ;

Ellis, Ian O. ;

Reis-Filho, Jorge S. .

MODERN PATHOLOGY, 2011, 24 (02) :157-167

[7] The causal relation between human papillomavirus and cervical cancer [J].

Bosch, FX ;

Lorincz, A ;

Muñoz, N ;

Meijer, CJLM ;

Shah, KV .

JOURNAL OF CLINICAL PATHOLOGY, 2002, 55 (04) :244-265

[8] Annotation of functional variation in personal genomes using RegulomeDB [J].

Boyle, Alan P. ;

Hong, Eurie L. ;

Hariharan, Manoj ;

Cheng, Yong ;

Schaub, Marc A. ;

Kasowski, Maya ;

Karczewski, Konrad J. ;

Park, Julie ;

Hitz, Benjamin C. ;

Weng, Shuai ;

Cherry, J. Michael ;

Snyder, Michael .

GENOME RESEARCH, 2012, 22 (09) :1790-1797

[9] Integrated genomic and molecular characterization of cervical cancer [J].

Burk, Robert D. ;

Chen, Zigui ;

Saller, Charles ;

Tarvin, Katherine ;

Carvalho, Andre L. ;

Scapulatempo-Neto, Cristovam ;

Silveira, Henrique C. ;

Fregnani, Jose H. ;

Creighton, Chad J. ;

Anderson, Matthew L. ;

Castro, Patricia ;

Wang, Sophia S. ;

Yau, Christina ;

Benz, Christopher ;

Robertson, A. Gordon ;

Mungall, Karen ;

Lim, Lynette ;

Bowlby, Reanne ;

Sadeghi, Sara ;

Brooks, Denise ;

Sipahimalani, Payal ;

Mar, Richard ;

Ally, Adrian ;

Clarke, Amanda ;

Mungall, Andrew J. ;

Tam, Angela ;

Lee, Darlene ;

Chuah, Eric ;

Schein, Jacqueline E. ;

Tse, Kane ;

Kasaian, Katayoon ;

Ma, Yussanne ;

Marra, Marco A. ;

Mayo, Michael ;

Balasundaram, Miruna ;

Thiessen, Nina ;

Dhalla, Noreen ;

Carlsen, Rebecca ;

Moore, Richard A. ;

Holt, Robert A. ;

Jones, Steven J. M. ;

Wong, Tina ;

Pantazi, Angeliki ;

Parfenov, Michael ;

Kucherlapati, Raju ;

Hadjipanayis, Angela ;

Seidman, Jonathan ;

Kucherlapati, Melanie ;

Ren, Xiaojia ;

Xu, Andrew W. .

NATURE, 2017, 543 (7645) :378-+

[10] The UK Biobank resource with deep phenotyping and genomic data [J].

Bycroft, Clare ;

Freeman, Colin ;

Petkova, Desislava ;

Band, Gavin ;

Elliott, Lloyd T. ;

Sharp, Kevin ;

Motyer, Allan ;

Vukcevic, Damjan ;

Delaneau, Olivier ;

O'Connell, Jared ;

Cortes, Adrian ;

Welsh, Samantha ;

Young, Alan ;

Effingham, Mark ;

McVean, Gil ;

Leslie, Stephen ;

Allen, Naomi ;

Donnelly, Peter ;

Marchini, Jonathan .

NATURE, 2018, 562 (7726) :203-+

← 1 2 3 4 5 6 7 →