Polygenic risk modeling for prediction of epithelial ovarian cancer risk

被引：35

作者：

Dareng, Eileen O. ^{[1
]}

Tyrer, Jonathan P. ^{[2
]}

Barnes, Daniel R. ^{[1
]}

Jones, Michelle R. ^{[3
]}

Yang, Xin ^{[1
]}

Aben, Katja K. H. ^{[4
,5
]}

Adank, Muriel A. ^{[6
]}

Agata, Simona ^{[7
]}

Andrulis, Irene L. ^{[8
,9
]}

Anton-Culver, Hoda ^{[10
]}

Antonenkova, Natalia N. ^{[11
]}

Aravantinos, Gerasimos ^{[12
]}

Arun, Banu K. ^{[13
]}

Augustinsson, Annelie ^{[14
]}

Balmana, Judith ^{[15
,16
]}

Bandera, Elisa, V ^{[17
]}

Barkardottir, Rosa B. ^{[18
,19
]}

Barrowdale, Daniel ^{[1
]}

Beckmann, Matthias W. ^{[20
]}

Beeghly-Fadiel, Alicia ^{[21
]}

Benitez, Javier ^{[22
,23
]}

Bermisheva, Marina ^{[24
]}

Bernardini, Marcus Q. ^{[25
]}

Bjorge, Line ^{[26
,27
]}

Black, Amanda ^{[28
]}

Bogdanova, Natalia, V ^{[11
,29
,30
]}

Bonanni, Bernardo ^{[31
]}

Borg, Ake ^{[32
,33
]}

Brenton, James D. ^{[34
]}

Budzilowska, Agnieszka ^{[35
]}

Butzow, Ralf ^{[36
]}

Buys, Saundra S. ^{[37
]}

Cai, Hui ^{[21
]}

Caligo, Maria A. ^{[38
]}

Campbell, Ian ^{[39
,40
]}

Cannioto, Rikki ^{[41
]}

Cassingham, Hayley ^{[42
]}

Chang-Claude, Jenny ^{[43
,44
]}

Chanock, Stephen J. ^{[45
]}

Chen, Kexin ^{[46
]}

Chiew, Yoke-Eng ^{[47
,48
]}

Chung, Wendy K. ^{[49
,50
]}

Claes, Kathleen B. M. ^{[51
]}

Colonna, Sarah ^{[37
]}

Cook, Linda S. ^{[57
,58
]}

Couch, Fergus J. ^{[59
]}

Daly, Mary B. ^{[60
]}

Dao, Fanny ^{[61
]}

Davies, Eleanor

de la Hoya, Miguel ^{[62
]}

机构：

[1] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[2] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[3] Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA

[4] Radboud Univ Nijmegen Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands

[5] Netherlands Comprehens Canc Org, Utrecht, Netherlands

[6] Antoni van Leeuwenhoek Hosp, Family Canc Clin, Netherlands Canc Inst, Amsterdam, Netherlands

[7] IRCCS, Immunol & Mol Oncol Unit, Veneto Inst Oncol IOV, Padua, Italy

[8] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[9] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[10] Univ Calif Irvine, Genet pidemiol Res Inst, Dept Epidemiol, Irvine, CA USA

[11] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, BELARUS

[12] Agii Anargiri Canc Hosp, Athens, Greece

[13] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[14] Lund Univ, Dept Canc Epidemiol, Clin Sci, Lund, Sweden

[15] Vall Hebron Inst Oncol, Hereditary Canc Genet Grp, Barcelona, Spain

[16] Univ Hosp Vall Hebron, Dept Med Oncol, Barcelona, Spain

[17] Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA

[18] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland

[19] Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik, Iceland

[20] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr ER EMN, Dept Gynecol & Obstet, Erlangen, Germany

[21] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Dept Med,Sch Med, Nashville, TN USA

[22] Biomed Network Rare Dis CIBERER, Madrid, Spain

[23] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid, Spain

[24] Russian Acad Sci, Inst Biochem & Genet, Ufa Fed Res Ctr, Ufa, Russia

[25] Univ Hlth Network, Princess Margaret Hosp, Div Gynecol Oncol, Toronto, ON, Canada

[26] Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway

[27] Univ Bergen, Ctr Canc Biomarkers CCBIO, Dept Clin Sci, Bergen, Norway

[28] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[29] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany

[30] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[31] European Inst Oncol IRCCS, Div Canc Prevent & Genet, IEO, Milan, Italy

[32] Lund Univ, Dept Oncol, Lund, Sweden

[33] Skane Univ Hosp, Dept Oncol, Lund, Sweden

[34] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[35] Maria Sklodowska Curie Natl Res Inst Oncol, Dept Pathol & Lab Diagnost, Warsaw, Poland

[36] Univ Helsinki, Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland

[37] Huntsman Canc Inst, Dept Med, Salt Lake City, UT USA

[38] Univ Hosp, SOD Genet Mol, Pisa, Italy

[39] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[40] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[41] Roswell Park Canc Inst, Canc Pathol & Prevent, Div Canc Prevent & Populat Sci, Buffalo, NY USA

[42] Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA

[43] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[44] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg UCCH, Canc Epidemiol Grp, Hamburg, Germany

[45] NCI, NIH, US Dept HHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[46] Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China

[47] Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia

[48] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia

[49] Columbia Univ, Dept Pediat, New York, NY USA

[50] Columbia Univ, Dept Med, New York, NY USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2022年 / 30卷 / 03期

关键词：

SUSCEPTIBILITY;

D O I：

10.1038/s41431-021-00987-7

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：

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

引用

页码：349 / 362

页数：14

共 31 条

[1] Performance and Robustness of Penalized and Unpenalized Methods for Genetic Prediction of Complex Human Disease
Abraham, Gad
Kowalczyk, Adam
Zobel, Justin
Inouye, Michael
[J]. GENETIC EPIDEMIOLOGY, 2013, 37 (02) : 184 - 195
[2] Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Barnes, Daniel R.
Rookus, Matti A.
McGuffog, Lesley
Leslie, Goska
Mooij, Thea M.
Dennis, Joe
Mavaddat, Nasim
Adlard, Julian
Ahmed, Munaza
Aittomaki, Kristiina
Andrieu, Nadine
Andrulis, Irene L.
Arnold, Norbert
Arun, Banu K.
Azzollini, Jacopo
Balmana, Judith
Barkardottir, Rosa B.
Barrowdale, Daniel
Benitez, Javier
Berthet, Pascaline
Bialkowska, Katarzyna
Blanco, Amie M.
Blok, Marinus J.
Bonanni, Bernardo
Boonen, Susanne E.
Borg, Ake
Bozsik, Aniko
Bradbury, Angela R.
Brennan, Paul
Brewer, Carole
Brunet, Joan
Buys, Saundra S.
Caldes, Trinidad
Caligo, Maria A.
Campbell, Ian
Christensen, Lise Lotte
Chung, Wendy K.
Claes, Kathleen B. M.
Colas, Chrystelle
Collonge-Rame, Marie-Agnes
Cook, Jackie
Daly, Mary B.
Davidson, Rosemarie
de la Hoya, Miguel
de Putter, Robin
Delnatte, Capucine
Devilee, Peter
Diez, Orland
Ding, Yuan Chun
Domchek, Susan M.
[J]. GENETICS IN MEDICINE, 2020, 22 (10) : 1653 - 1666
[3] The UK Biobank resource with deep phenotyping and genomic data
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
[J]. NATURE, 2018, 562 (7726) : 203 - +
[4] Polygenic prediction via Bayesian regression and continuous shrinkage priors
Ge, Tian
Chen, Chia-Yen
Ni, Yang
Feng, Yen-Chen Anne
Smoller, Jordan W.
[J]. NATURE COMMUNICATIONS, 2019, 10 (1)
[5] Polygenic risk scores outperform machine learning methods in predicting coronary artery disease status
Gola, Damian
Erdmann, Jeannette
Mueller-Myhsok, Bertram
Schunkert, Heribert
Koenig, Inke R.
[J]. GENETIC EPIDEMIOLOGY, 2020, 44 (02) : 125 - 138
[6] Extension of the bayesian alphabet for genomic selection
Habier, David
Fernando, Rohan L.
Kizilkaya, Kadir
Garrick, Dorian J.
[J]. BMC BIOINFORMATICS, 2011, 12
[7] Leveraging functional annotations in genetic risk prediction for human complex diseases
Hu, Yiming
Lu, Qiongshi
Powles, Ryan
Yao, Xinwei
Yang, Can
Fang, Fang
Xu, Xinran
Zhao, Hongyu
[J]. PLOS COMPUTATIONAL BIOLOGY, 2017, 13 (06)
[8] Evaluating the Utility of Polygenic Risk Scores in Identifying High-Risk Individuals for Eight Common Cancers
Jia, Guochong
Lu, Yingchang
Wen, Wanqing
Long, Jirong
Liu, Ying
Tao, Ran
Li, Bingshan
Denny, Joshua C.
Shu, Xiao-Ou
Zheng, Wei
[J]. JNCI CANCER SPECTRUM, 2020, 4 (03)
[9] Genetic epidemiology of ovarian cancer and prospects for polygenic risk prediction
Jones, Michelle R.
Kamara, Daniella
Karlan, Beth Y.
Pharoah, Paul D. P.
Gayther, Simon A.
[J]. GYNECOLOGIC ONCOLOGY, 2017, 147 (03) : 705 - 713
[10] Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions
Kar, Siddhartha P.
Berchuck, Andrew
Gayther, Simon A.
Goode, Ellen L.
Moysich, Kirsten B.
Pearce, Celeste Leigh
Ramus, Susan J.
Schildkraut, Joellen M.
Sellers, Thomas A.
Pharoah, Paul D. P.
[J]. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2018, 27 (04) : 395 - 404

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