TY - JOUR
T1 - Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients
AU - Macauda, Angelica
AU - Piredda, Chiara
AU - Clay-Gilmour, Alyssa I.
AU - Sainz, Juan
AU - Buda, Gabriele
AU - Markiewicz, Miroslaw
AU - Barington, Torben
AU - Ziv, Elad
AU - Hildebrandt, Michelle A.T.
AU - Belachew, Alem A.
AU - Varkonyi, Judit
AU - Prejzner, Witold
AU - Druzd-Sitek, Agnieszka
AU - Spinelli, John
AU - Andersen, Niels Frost
AU - Hofmann, Jonathan N.
AU - Dudziński, Marek
AU - Martinez-Lopez, Joaquin
AU - Iskierka-Jazdzewska, Elzbieta
AU - Milne, Roger L.
AU - Mazur, Grzegorz
AU - Giles, Graham G.
AU - Ebbesen, Lene Hyldahl
AU - Rymko, Marcin
AU - Jamroziak, Krzysztof
AU - Subocz, Edyta
AU - Reis, Rui Manuel
AU - Garcia-Sanz, Ramon
AU - Suska, Anna
AU - Haastrup, Eva Kannik
AU - Zawirska, Daria
AU - Grzasko, Norbert
AU - Vangsted, Annette Juul
AU - Dumontet, Charles
AU - Kruszewski, Marcin
AU - Dutka, Magdalena
AU - Camp, Nicola J.
AU - Waller, Rosalie G.
AU - Tomczak, Waldemar
AU - Pelosini, Matteo
AU - Raźny, Małgorzata
AU - Marques, Herlander
AU - Abildgaard, Niels
AU - Wątek, Marzena
AU - Jurczyszyn, Artur
AU - Brown, Elizabeth E.
AU - Berndt, Sonja
AU - Butrym, Aleksandra
AU - Vachon, Celine M.
AU - Norman, Aaron D.
AU - Slager, Susan L.
AU - Gemignani, Federica
AU - Canzian, Federico
AU - Campa, Daniele
N1 - Funding Information:
The authors thank all site investigators that contributed to the studies within the Multiple Myeloma Working Group (Interlymph Consortium), staff involved at each site and, most importantly, the study participants for their contributions that made our study possible. This work was partially supported by intramural funds of University of Pisa and DKFZ. This work was supported in part by the National Institute of Health/National Cancer Institute (R25 CA092049, P30 CA016672, R01 CA134674, P30 CA042014, R01 CA186646, R21 CA155951, U54 CA118948, P30 CA13148, R25 CA47888, R01 CA235026, R01 CA107476, R01 CA168762, P50 CA186781 and the NCI Intramural Research Program), Leukemia Lymphoma Society (6067-09), Huntsman Cancer Institute Pilot Funds, Utah Population Database, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah State Department of Health, University of Utah, Canadian Institutes of Health Research (Grant number 81274), VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council (Grants 209057, 396414, 1074383), Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database and the Mayo Clinic Cancer Center. Open Access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Gene 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.
AB - Gene 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.
KW - eQTL
KW - genetic polymorphisms
KW - multiple myeloma
KW - overall survival
KW - progression-free survival
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U2 - 10.1002/ijc.33547
DO - 10.1002/ijc.33547
M3 - Article
C2 - 33675538
AN - SCOPUS:85103377152
VL - 149
SP - 327
EP - 336
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -