Citations 2
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Cabrera-Serrano, Antonio José , Sánchez‐Maldonado, José Manuel , Macauda, Angelica , García-Martín, Paloma, Benavente, Yolanda , Landi, Stefano , Clay‐Gilmour, Alyssa , Niazi, Yasmeen , Espinet, Blanca , Rodríguez‐Sevilla, Juan José , Pérez, Eva María, Maffei, Rossana , Blanco, Gonzalo , Giaccherini, Matteo , Marasca, Roberto , López‐Nevot, Miguel Ángel , Thomsen, Hauke , Gámez, Irene, Campa, Daniele , Moreno, Vı́ctor , Sanjosé, Sílvia de , Marcos‐Gragera, Rafael , García‐Álvarez, María , Dierssen‐Sotos, Trinidad , Jerez, Andrés , Butrym, Aleksandra , Hemminki, Kari , Li, Yang , Berndt, Sonja I. , Casabonne, Delphine , Alcoceba, Miguel , Puiggros, Anna , Netea, Mihai G. , Försti, Asta , Canzian, Federico , Sáinz, Juan , Benavente, Yolanda , Landi, Stefano , Espinet, Blanca , Rodríguez-Sevilla, Juan José , Maffei, Rossana , Blanco, Gonzalo , Giaccherini, Matteo , Marasca, Roberto , López-Nevot, Miguel Ángel , Thomsen, Hauke , Moreno, Victor , Marcos-Gragera, Rafael , Dierssen-Sotos, Trinidad , Jerez, Andrés , Butrym, Aleksandra , Hemminki, Kari , Li, Yang , Alcoceba, Miguel , Puiggros, Anna , Försti, Asta , Canzian, Federico , Sainz, Juan , Horst, Rob ter , García-Martín, Paloma, Cerhan, James R. , Chen-Liang, Tzu-Hua , Norman, Aaron D. , Luppi, Mario , Slager, Susan L. , Netea, M. G.
International Journal of Molecular Sciences | April 28, 2023 | Volume: 24 | Issue: 9 | Pages: 8005
Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.
A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk
Dicanio, Marco, Giaccherini, Matteo , Clay‐Gilmour, Alyssa , Macauda, Angelica , Sáinz, Juan , Machiela, Mitchell J. , Rybicka‐Ramos, Malwina, Barington, Torben , Kumar, Shaji , Bhatti, Parveen , Brown, Elizabeth E. , Haastrup, Eva, Orlowski, Robert Z. , Dudziński, Marek , García‐Sánz, Ramón , Kruszewski, Marcin , Martínez‐López, Joaquín , Beider, Katia , Iskierka‐Jazdzewska, Elżbieta , Pelosini, Matteo , Berndt, Sonja I. , Raźny, Małgorzata , Collado, Pilar, Petrini, Mario , Butrym, Aleksandra , Ziv, Elad , Andersen, Niels Frost, Mazur, Grzegorz , Wątek, Marzena , Zawirska, Daria , Ebbesen, Lene Hyldahl, Gemignani, Federica , Várkonyi, Judit , Buda, Gabriele , Nagler, Arnon, Druzd‐Sitek, Agnieszka , Wu, Xifeng , Kádár, Katalin , Camp, Nicola J. , Grząśko, Norbert , Waller, Rosalie, Vachon, Celine M. , Campa, Daniele , Martinez-Lopez, Joaquin , Waller, Rosalie G. , Griffin, R. L. , Beider, Katia , Lesueur, Fabienne , Hildebrandt, Michelle A T , Vachon, Celine, Campa, Daniele , Orlowski, Robert Z. , Martinez-Lopez, Joaquin , Butrym, Aleksandra , Garcia-Sanz, Ramon , Bhatti, Parveen , Ziv, Elad , Waller, Rosalie G , Machiela, Mitchell J , Sainz, Juan , Watek, Marzena , Iskierka-Jazdzewska, Elżbieta , Martinez-Lopez, Joaquin , Mazur, Grzegorz , Giaccherini, Matteo , Griffin, Rosalie , Norman, Aaron D. , Tyczyńska, Agata , Chanock, Stephen Jacob , Cozen, Wendy , Suska, Anna , Jamroziak, Krzysztof , Rajkumar, S. Vincent , Jurczyszyn, Artur , Vangsted, Annette Juul , Collado, Pilar Garrido, Vogel, Ulla , Hofmann, Jonathan N. , Slager, Susan L. , Subocz, Edyta , Giles, Graham G. , Lesueur, Fabienne , Hildebrandt, Michelle A.T. , Marques, Herlander , Dumontet, Charles , Nagler, Arnon , Vachon, Celine M. , Canzian, Federico
International Journal of Cancer | September 9, 2022 | Volume: 152 | Issue: 2 | Pages: 239-248
AbstractPleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome‐wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4‐rs34517439‐A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13‐1.32, P = 4.81 × 10−7). rs34517439‐A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA‐binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4‐rs34517439 as a potentially novel MM risk locus.