A polygenic risk score for multiple myeloma risk prediction
Federico Canzian
(1)
,
Chiara Piredda
(1, 2)
,
Angelica Macauda
(1, 2)
,
Daria Zawirska
(3)
,
Niels Frost Andersen
(4)
,
Arnon Nagler
(5)
,
Jan Maciej Zaucha
(6)
,
Grzegorz Mazur
(7)
,
Charles Dumontet
(8, 9)
,
Marzena Wątek
(10)
,
Krzysztof Jamroziak
(11)
,
Juan Sainz
(12, 13)
,
Judit Varkonyi
(14)
,
Aleksandra Butrym
(7)
,
Katia Beider
(5)
,
Niels Abildgaard
(15)
,
Fabienne Lesueur
(16)
,
Marek Dudziński
(17)
,
Annette Juul Vangsted
(18)
,
Matteo Pelosini
(2)
,
Edyta Subocz
(19)
,
Mario Petrini
(2)
,
Gabriele Buda
(2)
,
Małgorzata Raźny
(20)
,
Federica Gemignani
(2)
,
Herlander Marques
(21)
,
Enrico Orciuolo
(2)
,
Katalin Kadar
(14)
,
Artur Jurczyszyn
(22)
,
Agnieszka Druzd-Sitek
(23)
,
Ulla Vogel
(24)
,
Helle Vibeke Andersen
(25)
,
Rui Manuel Reis
(26, 21, 27)
,
Anna Suska
(22)
,
Hervé Avet Loiseau
(28)
,
Marcin Kruszewski
(29)
,
Waldemar Tomczak
(30)
,
Marcin Rymko
(31)
,
Stephane Minvielle
(32)
,
Daniele Campa
(2)
1
GEP / DKFZ -
Genomic Epidemiology Group [Heidelberg, Germany]
2 University of Pisa - Università di Pisa
3 SUK - University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland]
4 Aarhus University Hospital
5 Chaim Sheba Medical Center
6 SH - Sea Hospital [Gdynia, Poland]
7 Wrocław Medical University
8 HCL - Hospices Civils de Lyon
9 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
10 Holycross Cancer Center of Kelce, Hematology Clinic, Kielce
11 IHTM - Institute of Hematology and Transfusion Medicine [Warsaw, Poland]
12 GENYO - Centre for Genomics and Oncological Research Pfizer [Granada, Spain]
13 HUVN - Hospital Universitario Virgen de las Nieves [Granada, Spain]
14 Semmelweis University [Budapest]
15 OUH - Odense University Hospital
16 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
17 TH1 - Teaching Hospital No 1 [Rzeszów, Poland]
18 UCPH - University of Copenhagen = Københavns Universitet
19 MIM - Military Institute of Medicine [Warsaw, Poland]
20 RSH - Rydygier Specialistic Hospital [Cracow, Poland]
21 University of Minho [Braga]
22 UJ - Uniwersytet Jagielloński w Krakowie = Jagiellonian University
23 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
24 NRCWE - The National Research Center for Work Environment [Copenhagen, Denmark]
25 SDU - University of Southern Denmark
26 AL - ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal]
27 BCH - Barretos Cancer Hospital [São Paulo, Brazil]
28 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
29 UHB - University Hospital Bydgoszcz [Bydgoszcz, Poland]
30 Medical University of Lublin
31 NCTH - N. Copernicus Town Hospital [Torun, Poland]
32 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
2 University of Pisa - Università di Pisa
3 SUK - University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland]
4 Aarhus University Hospital
5 Chaim Sheba Medical Center
6 SH - Sea Hospital [Gdynia, Poland]
7 Wrocław Medical University
8 HCL - Hospices Civils de Lyon
9 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
10 Holycross Cancer Center of Kelce, Hematology Clinic, Kielce
11 IHTM - Institute of Hematology and Transfusion Medicine [Warsaw, Poland]
12 GENYO - Centre for Genomics and Oncological Research Pfizer [Granada, Spain]
13 HUVN - Hospital Universitario Virgen de las Nieves [Granada, Spain]
14 Semmelweis University [Budapest]
15 OUH - Odense University Hospital
16 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
17 TH1 - Teaching Hospital No 1 [Rzeszów, Poland]
18 UCPH - University of Copenhagen = Københavns Universitet
19 MIM - Military Institute of Medicine [Warsaw, Poland]
20 RSH - Rydygier Specialistic Hospital [Cracow, Poland]
21 University of Minho [Braga]
22 UJ - Uniwersytet Jagielloński w Krakowie = Jagiellonian University
23 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
24 NRCWE - The National Research Center for Work Environment [Copenhagen, Denmark]
25 SDU - University of Southern Denmark
26 AL - ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal]
27 BCH - Barretos Cancer Hospital [São Paulo, Brazil]
28 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
29 UHB - University Hospital Bydgoszcz [Bydgoszcz, Poland]
30 Medical University of Lublin
31 NCTH - N. Copernicus Town Hospital [Torun, Poland]
32 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
Federico Canzian
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- Function : Correspondent author
- PersonId : 908773
Connectez-vous pour contacter l'auteur
Arnon Nagler
- Function : Author
- PersonId : 777286
- ORCID : 0000-0002-0763-1265
Fabienne Lesueur
- Function : Author
- PersonId : 766610
- ORCID : 0000-0001-7404-4549
- IdRef : 165329939
Federica Gemignani
- Function : Author
- PersonId : 771791
- ORCID : 0000-0003-1297-0701
Marcin Kruszewski
- Function : Author
- PersonId : 847006
Stephane Minvielle
- Function : Author
- PersonId : 738362
- IdHAL : stephane-minvielle
- ORCID : 0000-0003-1389-312X
- IdRef : 032987552
Abstract
There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genomewide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p = 3.55 × 10−15 for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p = 1.62 × 10−13 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.
Domains
Cancer
Origin : Publication funded by an institution