Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

被引：2

作者：

Purdue, Mark P. ^{[1
]}

Dutta, Diptavo ^{[2
]}

Machiela, Mitchell J. ^{[2
]}

Gorman, Bryan R. ^{[3
]}

Winter, Timothy ^{[4
]}

Okuhara, Dayne ^{[3
]}

Cleland, Sara ^{[3
]}

Ferreiro-Iglesias, Aida ^{[5
]}

Scheet, Paul ^{[6
]}

Liu, Aoxing ^{[7
,8
,9
]}

Wu, Chao ^{[10
]}

Antwi, Samuel O. ^{[11
]}

Larkin, James ^{[12
]}

Zequi, Stenio C. ^{[13
,14
,15
,16
]}

Sun, Maxine ^{[17
]}

Hikino, Keiko ^{[18
]}

Hajiran, Ali ^{[19
]}

Lawson, Keith A. ^{[20
]}

Carcano, Flavio ^{[21
]}

Blanchet, Odile ^{[22
]}

Shuch, Brian ^{[23
]}

Nepple, Kenneth G. ^{[24
]}

Margue, Gaelle ^{[25
]}

Sundi, Debasish ^{[26
]}

Diver, W. Ryan ^{[27
]}

Folgueira, Maria A. A. K. ^{[28
,29
]}

van Bokhoven, Adrie ^{[30
]}

Neffa, Florencia ^{[31
]}

Brown, Kevin M. ^{[32
]}

Hofmann, Jonathan N. ^{[1
]}

Rhee, Jongeun ^{[1
]}

Yeager, Meredith ^{[33
]}

Cole, Nathan R. ^{[33
]}

Hicks, Belynda D. ^{[33
]}

Manning, Michelle R. ^{[33
]}

Hutchinson, Amy A. ^{[33
]}

Rothman, Nathaniel ^{[1
]}

Huang, Wen-Yi ^{[34
]}

Linehan, W. Marston ^{[35
]}

Lori, Adriana ^{[27
]}

Ferragu, Matthieu ^{[36
]}

Zidane-Marinnes, Merzouka ^{[37
]}

Serrano, Sergio V. ^{[21
]}

Magnabosco, Wesley J. ^{[38
]}

Vilas, Ana ^{[39
]}

Decia, Ricardo ^{[40
]}

Carusso, Florencia ^{[31
]}

Graham, Laura S. ^{[41
]}

Anderson, Kyra ^{[42
]}

Bilen, Mehmet A. ^{[43
]}

机构：

[1] Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Rockville, MD 20850 USA

[2] Natl Canc Inst, Div Canc Epidemiol & Genet, Integrat Tumor Epidemiol Branch, Rockville, MD USA

[3] Booz Allen Hamilton Inc, Mclean, VA USA

[4] Natl Canc Inst, Div Canc Epidemiol & Genet, Lab Genet Susceptibil, Rockville, MD 20850 USA

[5] Int Agcy Res Canc, Genom Epidemiol Branch, Lyon, France

[6] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Dept Epidemiol, Houston, TX USA

[7] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

[8] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA USA

[9] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[10] Temple Hlth, Fox Chase Canc Ctr, Biosample Repository, Philadelphia, PA USA

[11] Mayo Clin, Dept Quantitat Hlth Sci, Jacksonville, FL USA

[12] Royal Marsden NHS Fdn Trust, Dept Med Oncol, London, England

[13] AC Camargo Canc Ctr, Dept Urol, Sao Paulo, Brazil

[14] Natl Inst Sci & Technol Oncogen & Therape Innovat, Sao Paulo, Brazil

[15] Latin Amer Renal Canc Grp, Sao Paulo, Brazil

[16] Sao Paulo Fed Univ, Div Urol, Dept Surg, Sao Paulo, Brazil

[17] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

[18] RIKEN Ctr Integrat Med Sci, Lab Pharmacogen, Yokohama, Kanagawa, Japan

[19] West Virginia Univ, Div Urol Oncol, Dept Urol, Canc Inst, Morgantown, WV USA

[20] Univ Hlth Network, Div Urol, Princess Margaret Canc Ctr, Dept Surg Oncol, Toronto, ON, Canada

[21] Barretos Canc Hosp, Dept Med Oncol, Barretos, Brazil

[22] CHU Angers, Biobank Resource Ctr, Angers, France

[23] UCLA, Dept Urol, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA

[24] Univ Iowa, Holden Comprehens Canc Ctr, Dept Urol, Iowa City, IA USA

[25] CHU Bordeaux, Dept Urol, Bordeaux, France

[26] Ohio State Univ, Dept Urol, Wexner Med Ctr, Columbus, OH USA

[27] Amer Canc Soc, Dept Populat Sci, Atlanta, GA USA

[28] Univ Sao Paulo, Ctr Invest Translac Oncol, Comprehens Ctr Precis Oncol C2PO, Dept Radiol,Inst Canc Estado Sao Paulo,Fac Med, Sao Paulo, Brazil

[29] Univ Sao Paulo, Ctr Invest Translac Oncol, Comprehens Ctr Precis Oncol C2PO, Dept Oncol,Inst Canc Estado Sao Paulo,Fac Med, Sao Paulo, Brazil

[30] Univ Colorado Anschutz Med Campus, Dept Pathol, Aurora, CO USA

[31] Hosp Mil, Tumor Bank, Montevideo, Uruguay

[32] Natl Canc Inst, Div Canc Epidemiol & Genet, Lab Translat Genom, Rockville, MD USA

[33] Frederick Natl Lab, Canc Genom Res Lab, Rockville, MD USA

[34] Natl Canc Inst, Div Canc Epidemiol & Genet, Metab Epidemiol Branch, Rockville, MD USA

[35] Natl Canc Inst, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD USA

[36] CHU Angers, Dept Urol, Angers, France

[37] CHU Angers, Dept Pathol, Angers, France

[38] Barretos Canc Hosp, Dept Urol, Barretos, Brazil

[39] Hosp Pasteur, Dept Pathol, Montevideo, Uruguay

[40] Hosp Pasteur, Department Urol, Montevideo, Uruguay

[41] Univ Colorado Anschutz Med Campus, Div Med Oncol, Dept Med, Aurora, CO USA

[42] Univ Colorado Anschutz Med Campus, Oncol Clin Res Support Team, Aurora, CO USA

[43] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA USA

[44] Emory Univ, Winship Canc Inst, Dept Surg, Sch Med, Atlanta, GA USA

[45] CHU Bordeaux, Biobank, Bordeaux Biotheque Sante, Bordeaux, France

[46] Observat & Pragmat Res Inst Pte Ltd, Singapore, Singapore

[47] Univ Leeds, Leeds Inst Med Res St Jamess, Leeds, W Yorkshire, England

[48] Univ Leeds, Leeds Inst Med Res St Jamess, Dept Oncol, Leeds, W Yorkshire, England

[49] Newcastle Hosp NHS Fdn Trust, Dept Urol, Newcastle Upon Tyne, Tyne & Wear, England

[50] Western Gen Hosp NHS Lothian, Dept Urol, Edinburgh, Midlothian, Scotland

来源：

NATURE GENETICS | 2024年

基金：

美国国家卫生研究院;

关键词：

RENAL-CELL CARCINOMA; VARIANTS; LOCI; HERITABILITY; METAANALYSIS; EXPRESSION; BINDING; TUMORS; RISK;

D O I：

10.1038/s41588-024-01725-7

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

引用

页码：809 / 818

页数：17

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