Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients

Angelica Macauda, Chiara Piredda, Alyssa I. Clay-Gilmour, Juan Sainz, Gabriele Buda, Miroslaw Markiewicz, Torben Barington, Elad Ziv, Michelle A.T. Hildebrandt, Alem A. Belachew, Judit Varkonyi, Witold Prejzner, Agnieszka Druzd-Sitek, John Spinelli, Niels Frost Andersen, Jonathan N. Hofmann, Marek Dudziński, Joaquin Martinez-Lopez, Elzbieta Iskierka-Jazdzewska, Roger L. MilneGrzegorz Mazur, Graham G. Giles, Lene Hyldahl Ebbesen, Marcin Rymko, Krzysztof Jamroziak, Edyta Subocz, Rui Manuel Reis, Ramon Garcia-Sanz, Anna Suska, Eva Kannik Haastrup, Daria Zawirska, Norbert Grzasko, Annette Juul Vangsted, Charles Dumontet, Marcin Kruszewski, Magdalena Dutka, Nicola J. Camp, Rosalie G. Waller, Waldemar Tomczak, Matteo Pelosini, Małgorzata Raźny, Herlander Marques, Niels Abildgaard, Marzena Wątek, Artur Jurczyszyn, Elizabeth E. Brown, Sonja Berndt, Aleksandra Butrym, Celine M. Vachon, Aaron D. Norman, Susan L. Slager, Federica Gemignani, Federico Canzian, Daniele Campa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - 2021

Keywords

  • eQTL
  • genetic polymorphisms
  • multiple myeloma
  • overall survival
  • progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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