Citations 2
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.
Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients
Macauda, Angelica , Piredda, Chiara , Clay‐Gilmour, Alyssa , Sáinz, Juan , Buda, Gabriele , Markiewicz, Mirosław , Barington, Torben , Ziv, Elad , Hildebrandt, Michelle A.T. , Belachew, Alem A. , Várkonyi, Judit , Prejzner, Witold , Druzd‐Sitek, Agnieszka , Spinelli, John J. , Andersen, Niels Frost, Dudziński, Marek , Martínez‐López, Joaquín , Iskierka‐Jazdzewska, Elżbieta , Mazur, Grzegorz , Ebbesen, Lene Hyldahl, Rymko, Marcin , Subocz, Edyta , Reis, Rui Manuel , García‐Sánz, Ramón , Suska, Anna , Haastrup, Eva, Zawirska, Daria , Grząśko, Norbert , Kruszewski, Marcin , Dutka, Magdalena , Camp, Nicola J. , Waller, Rosalie, Pelosini, Matteo , Raźny, Małgorzata , Abildgaard, Niels , Wątek, Marzena , Brown, Elizabeth E. , Berndt, Sonja I. , Butrym, Aleksandra , Vachon, Celine M. , Gemignani, Federica , Campa, Daniele , Martinez-Lopez, Joaquin , Waller, Rosalie G. , Griffin, R. L. , Canzian, Federico , Campa, Daniele , Martinez-Lopez, Joaquin , Butrym, Aleksandra , Reis, Rui Manuel , Garcia-Sanz, Ramon , Ziv, Elad , Waller, Rosalie G , Rymko, Marcin , Subocz, Edyta , Tomczak, Waldemar , Sainz, Juan , Watek, Marzena , Iskierka-Jazdzewska, Elżbieta , Martinez-Lopez, Joaquin , Mazur, Grzegorz , Hildebrandt, Michelle A T , Markiewicz, Miroslaw , Macauda, Angelica , Griffin, Rosalie , Hofmann, Jonathan N. , Milne, Roger L. , Giles, Graham G. , Jamroziak, Krzysztof , Vangsted, Annette Juul , Dumontet, Charles , Tomczak, Waldemar , Marques, Herlander , Jurczyszyn, Artur , Vachon, Celine M. , Norman, Aaron D. , Slager, Susan L. , Canzian, Federico
International Journal of Cancer | March 6, 2021 | Volume: 149 | Issue: 2 | Pages: 327-336
AbstractGene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype‐tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10−7 either in EBV‐transformed B‐lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression‐free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4‐rs1992292, TBRG4‐rs2287535 and ENTPD1‐rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta‐analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4‐rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04‐1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.