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^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

2 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cancer Epidemiology Biomarkers and Prevention
Vol/bind	31
Udgave nummer	9
Sider (fra-til)	1863-1866
ISSN	1055-9965
DOI	https://doi.org/10.1158/1055-9965.EPI-22-0043
Status	Udgivet - 2022

Bibliografisk note

Publisher Copyright:
© 2022 American Association for Cancer Research.

Adgang til dokumentet

10.1158/1055-9965.EPI-22-0043

Citationsformater

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

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

I: Cancer Epidemiology Biomarkers and Prevention, Bind 31, Nr. 9, 2022, s. 1863-1866.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, bind 31, nr. 9, s. 1863-1866. https://doi.org/10.1158/1055-9965.EPI-22-0043

MacAuda, Angelica ; Clay-Gilmour, Alyssa ; Hielscher, Thomas ; Hildebrandt, Michelle A.T. ; Kruszewski, Marcin ; Orlowski, Robert Z. ; Kumar, Shaji K. ; Ziv, Elad ; Orciuolo, Enrico ; Brown, Elizabeth E. ; Försti, Asta ; Waller, Rosalie G. ; MacHiela, Mitchell J. ; Chanock, Stephen J. ; Camp, Nicola J. ; Rymko, Marcin ; Raźny, Małgorzata ; Cozen, Wendy ; Várkonyi, Judit ; Piredda, Chiara ; Pelosini, Matteo ; Belachew, Alem A. ; Subocz, Edyta ; Hemminki, Kari ; Rybicka-Ramos, Malwina ; Giles, Graham G. ; Milne, Roger L. ; Hofmann, Jonathan N. ; Zaucha, Jan Mac Iej ; Vangsted, Annette Juul ; Goldschmidt, Hartmut ; Rajkumar, S. Vincent ; Tomczak, Waldemar ; Sainz, Juan ; Butrym, Aleksandra ; Watek, Marzena ; Iskierka-Jazdzewska, Elzbieta ; Buda, Gabriele ; Robinson, Dennis P. ; Jurczyszyn, Artur ; Dudzinski, Marek ; Martinez-Lopez, Joaquin ; Sinnwell, Jason P. ; Slager, Susan L. ; Jamroziak, Krzysztof ; Reis, Rui Manuel Vieira ; Weinhold, Niels ; Bhatti, Parveen ; Carvajal-Carmona, Luis G. ; Zawirska, Daria ; Norman, Aaron D. ; Mazur, Grzegorz ; Berndt, Sonja I. ; Campa, Daniele ; Vachon, Celine M. ; Canzian, Federico. / Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?. I: Cancer Epidemiology Biomarkers and Prevention. 2022 ; Bind 31, Nr. 9. s. 1863-1866.

@article{7efa12e6135c427491017f4f57484e1e,

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 = "Funding Information: of the study. J.M. Zaucha reports non-financial support from Roche; personal fees from Abbvie, Takeda, Jansssen; grants from BMS outside the submitted work. H. Goldschmidt reports grants, personal fees, and other support from Amgen, BMS, Celgene, Chugai, Janssen, Sanofi; other support from Incyte, Molecular Partners, MSD, Mundipharma GmbH, Takeda, Adaptive Biotechnology; personal fees and other support from Novartis; and personal fees from GSK outside the submitted work. E. Iskierka-Jazdzewska reports personal fees and non-financial support from Sandoz, Roche, Novartis, and Janssen; personal fees from AstraZeneca, Celgene outside the submitted work. C.M. Vachon reports other support from Mayo Clinic Cancer Center and grants from NCI during the conduct of the study. No disclosures were reported by the other authors. Funding Information: R.Z. Orlowski reports grants from Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma; other support from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, and Takeda Pharmaceuticals North America, Inc.; and personal fees from Abbvie, Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squib, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda Pharmaceuticals North America, Inc. outside the submitted work; and R.Z. Orlowski is a founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current article. S.K. Kumar reports grants from NCI during the conduct of the study; and research funding for clinical trials to the institution: Abbvie, Amgen, Allogene, AstraZeneca, BMS, Carsgen, GSK, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, Molecular Templates; reports consulting/advisory board participation: (with no personal payments) Abbvie, Amgen, BMS, Janssen, Roche-Gen-entech, Takeda, AstraZeneca, Bluebird Bio, Epizyme, Secura Biotherapeutics, Mon-terosa therapeutics, Trillium, Loxo Oncology, K36, Sanofi, ArcellX, and (with personal payment) Oncopeptides, Beigene, Antengene, GLH Pharma. E. Ziv reports grants from The UCSF Stephen & Nancy Grand Multiple Myeloma Translational Initiative and grants from NIH/NCI during the conduct of the study. G.G. Giles reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. R.L. Milne reports grants from NHMRC during the conduct ",

year = "2022",

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

language = "English",

volume = "31",

pages = "1863--1866",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",