Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Angelica MacAuda; Alyssa Clay-Gilmour; Thomas Hielscher; Michelle A.T. Hildebrandt; Marcin Kruszewski; Robert Z. Orlowski; Shaji K. Kumar; Elad Ziv; Enrico Orciuolo; Elizabeth E. Brown; Asta Försti; Rosalie G. Waller; Mitchell J. MacHiela; Stephen J. Chanock; Nicola J. Camp; Marcin Rymko; Małgorzata Raźny; Wendy Cozen; Judit Várkonyi; Chiara Piredda; Matteo Pelosini; Alem A. Belachew; Edyta Subocz; Kari Hemminki; Malwina Rybicka-Ramos; Graham G. Giles; Roger L. Milne; Jonathan N. Hofmann; Jan Mac Iej Zaucha; Annette Juul Vangsted; Hartmut Goldschmidt; S. Vincent Rajkumar; Waldemar Tomczak; Juan Sainz; Aleksandra Butrym; Marzena Watek; Elzbieta Iskierka-Jazdzewska; Gabriele Buda; Dennis P. Robinson; Artur Jurczyszyn; Marek Dudzinski; Joaquin Martinez-Lopez; Jason P. Sinnwell; Susan L. Slager; Krzysztof Jamroziak; Rui Manuel Vieira Reis; Niels Weinhold; Parveen Bhatti; Luis G. Carvajal-Carmona; Daria Zawirska; Aaron D. Norman; Grzegorz Mazur; Sonja I. Berndt; Daniele Campa; Celine M. Vachon; Federico Canzian

doi:10.1158/1055-9965.EPI-22-0043

Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Angelica MacAuda, Alyssa Clay-Gilmour, Thomas Hielscher, Michelle A.T. Hildebrandt, Marcin Kruszewski, Robert Z. Orlowski, Shaji K. Kumar, Elad Ziv, Enrico Orciuolo, Elizabeth E. Brown, Asta Försti, Rosalie G. Waller, Mitchell J. MacHiela, Stephen J. Chanock, Nicola J. Camp, Marcin Rymko, Małgorzata Raźny, Wendy Cozen, Judit Várkonyi, Chiara PireddaMatteo Pelosini, Alem A. Belachew, Edyta Subocz, Kari Hemminki, Malwina Rybicka-Ramos, Graham G. Giles, Roger L. Milne, Jonathan N. Hofmann, Jan Mac Iej Zaucha, Annette Juul Vangsted, Hartmut Goldschmidt, S. Vincent Rajkumar, Waldemar Tomczak, Juan Sainz, Aleksandra Butrym, Marzena Watek, Elzbieta Iskierka-Jazdzewska, Gabriele Buda, Dennis P. Robinson, Artur Jurczyszyn, Marek Dudzinski, Joaquin Martinez-Lopez, Jason P. Sinnwell, Susan L. Slager, Krzysztof Jamroziak, Rui Manuel Vieira Reis, Niels Weinhold, Parveen Bhatti, Luis G. Carvajal-Carmona, Daria Zawirska, Aaron D. Norman, Grzegorz Mazur, Sonja I. Berndt, Daniele Campa, Celine M. Vachon, Federico Canzian

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

Original language	English (US)
Pages (from-to)	1863-1866
Number of pages	4
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	31
Issue number	9
DOIs	https://doi.org/10.1158/1055-9965.EPI-22-0043
State	Published - Sep 2022

ASJC Scopus subject areas

General Medicine

Access to Document

10.1158/1055-9965.EPI-22-0043

Cite this

MacAuda, A., Clay-Gilmour, A., Hielscher, T., Hildebrandt, M. A. T., Kruszewski, M., Orlowski, R. Z., Kumar, S. K., Ziv, E., Orciuolo, E., Brown, E. E., Försti, A., Waller, R. G., MacHiela, M. J., Chanock, S. J., Camp, N. J., Rymko, M., Raźny, M., Cozen, W., Várkonyi, J., ... Canzian, F. (2022). Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma? Cancer Epidemiology Biomarkers and Prevention, 31(9), 1863-1866. https://doi.org/10.1158/1055-9965.EPI-22-0043

MacAuda, A, Clay-Gilmour, A, Hielscher, T, Hildebrandt, MAT, Kruszewski, M, Orlowski, RZ, Kumar, SK, Ziv, E, Orciuolo, E, Brown, EE, Försti, A, Waller, RG, MacHiela, MJ, Chanock, SJ, Camp, NJ, Rymko, M, Raźny, M, Cozen, W, Várkonyi, J, Piredda, C, Pelosini, M, Belachew, AA, Subocz, E, Hemminki, K, Rybicka-Ramos, M, Giles, GG, Milne, RL, Hofmann, JN, Zaucha, JMI, Vangsted, AJ, Goldschmidt, H, Rajkumar, SV, Tomczak, W, Sainz, J, Butrym, A, Watek, M, Iskierka-Jazdzewska, E, Buda, G, Robinson, DP, Jurczyszyn, A, Dudzinski, M, Martinez-Lopez, J, Sinnwell, JP, Slager, SL, Jamroziak, K, Reis, RMV, Weinhold, N, Bhatti, P, Carvajal-Carmona, LG, Zawirska, D, Norman, AD, Mazur, G, Berndt, SI, Campa, D, Vachon, CM & Canzian, F 2022, 'Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?', Cancer Epidemiology Biomarkers and Prevention, vol. 31, no. 9, pp. 1863-1866. https://doi.org/10.1158/1055-9965.EPI-22-0043

@article{c151b7c3e119489f99a9e1cf536421de,

title = "Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?",

abstract = "Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.",

author = "Angelica MacAuda and Alyssa Clay-Gilmour and Thomas Hielscher and Hildebrandt, {Michelle A.T.} and Marcin Kruszewski and Orlowski, {Robert Z.} and Kumar, {Shaji K.} and Elad Ziv and Enrico Orciuolo and Brown, {Elizabeth E.} and Asta F{\"o}rsti and Waller, {Rosalie G.} and MacHiela, {Mitchell J.} and Chanock, {Stephen J.} and Camp, {Nicola J.} and Marcin Rymko and Ma{\l}gorzata Ra{\'z}ny and Wendy Cozen and Judit V{\'a}rkonyi and Chiara Piredda and Matteo Pelosini and Belachew, {Alem A.} and Edyta Subocz and Kari Hemminki and Malwina Rybicka-Ramos and Giles, {Graham G.} and Milne, {Roger L.} and Hofmann, {Jonathan N.} and Zaucha, {Jan Mac Iej} and Vangsted, {Annette Juul} and Hartmut Goldschmidt and Rajkumar, {S. Vincent} and Waldemar Tomczak and Juan Sainz and Aleksandra Butrym and Marzena Watek and Elzbieta Iskierka-Jazdzewska and Gabriele Buda and Robinson, {Dennis P.} and Artur Jurczyszyn and Marek Dudzinski and Joaquin Martinez-Lopez and Sinnwell, {Jason P.} and Slager, {Susan L.} and Krzysztof Jamroziak and Reis, {Rui Manuel Vieira} and Niels Weinhold and Parveen Bhatti and Carvajal-Carmona, {Luis G.} and Daria Zawirska and Norman, {Aaron D.} and Grzegorz Mazur and Berndt, {Sonja I.} and Daniele Campa and Vachon, {Celine M.} and Federico Canzian",

note = "Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research.",

year = "2022",

month = sep,

doi = "10.1158/1055-9965.EPI-22-0043",

language = "English (US)",

volume = "31",

pages = "1863--1866",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",