Meta-Analysis

. 2022 Sep 2;31(9):1863-1866.

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

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

Angelica Macauda^#^{1

2}, Alyssa Clay-Gilmour^#³, Thomas Hielscher⁴, Michelle A T Hildebrandt⁵, Marcin Kruszewski⁶, Robert Z Orlowski⁵, Shaji K Kumar⁷, Elad Ziv⁸, Enrico Orciuolo⁹, Elizabeth E Brown¹⁰, Asta Försti^{11

12}, Rosalie G Waller¹³, Mitchell J Machiela¹⁴, Stephen J Chanock¹⁴, Nicola J Camp¹⁵, Marcin Rymko¹⁶, Małgorzata Raźny¹⁷, Wendy Cozen¹⁸, Judit Várkonyi¹⁹, Chiara Piredda¹, Matteo Pelosini⁹, Alem A Belachew⁵, Edyta Subocz²⁰, Kari Hemminki^{21

22}, Malwina Rybicka-Ramos²³, Graham G Giles^{24

25

26}, Roger L Milne^{24

25

26}, Jonathan N Hofmann¹⁴, Jan Maciej Zaucha²⁷, Annette Juul Vangsted²⁸, Hartmut Goldschmidt²⁹, S Vincent Rajkumar⁷, Waldemar Tomczak³⁰, Juan Sainz^{31

32}, Aleksandra Butrym³³, Marzena Watek³⁴, Elżbieta Iskierka-Jazdzewska³⁵, Gabriele Buda⁹, Dennis P Robinson¹³, Artur Jurczyszyn³⁶, Marek Dudziński³⁷, Joaquin Martinez-Lopez³⁸, Jason P Sinnwell¹³, Susan L Slager¹³, Krzysztof Jamroziak³⁹, Rui Manuel Vieira Reis^{40

41}, Niels Weinhold^{29

42}, Parveen Bhatti^{43

44}, Luis G Carvajal-Carmona^{45

46

47}, Daria Zawirska⁴⁸, Aaron D Norman¹³, Grzegorz Mazur³³, Sonja I Berndt¹⁴, Daniele Campa^#², Celine M Vachon^#⁴⁹, Federico Canzian^#¹

Affiliations

¹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Biology, University of Pisa, Pisa, Italy.
³ Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Greenville, South Carolina.
⁴ Division of Biostatistics, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
⁵ Department of Lymphoma - Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁶ Department of Hematology University Hospital Bydgoszcz, Bydgoszcz, Poland.
⁷ Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
⁸ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
⁹ Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
¹⁰ Department of Pathology, School of Medicine, University of Alabama, Birmingham, Alabama.
¹¹ Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
¹² Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
¹³ Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
¹⁴ Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
¹⁵ Division of Hematology and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
¹⁶ Department of Haematology and Bone Marrow Transplantation, SSM im. M. Kopernika, Torun, Poland.
¹⁷ Department of Hematology, Rydygier Hospital, Cracow, Poland.
¹⁸ Division of Hematology/Oncology, Department of Medicine, School of Medicine, Department of Pathology, School of Medicine, Susan and Henry Samueli College of Health Sciences, Chao Family Comprehensive Cancer Center, University of California at Irvine, California.
¹⁹ Department of Hematology and Internal Medicine, Semmelweis University, Budapest, Hungary.
²⁰ Department of Hematology, Military Institute of Medicine, Warsaw, Poland.
²¹ Biomedical Center, Faculty of Medicine, Charles University in Pilsen, Pilsen, Czech Republic.
²² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²³ Department of Hematology Specialist Hospital No. 1 in Bytom, Bytom, Poland.
²⁴ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
²⁵ Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
²⁶ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²⁷ Department of Hematology and Transplantology, Medical Univeristy of Gdańsk, Gdańsk, Poland.
²⁸ Department of Haematology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
²⁹ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
³⁰ Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Poland.
³¹ Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Granada, Spain.
³² Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.
³³ Department of Internal and Occupational Diseases, Medical University Wroclaw, Wroclaw, Poland.
³⁴ Hematology Clinic, Holycross Cancer Center, Kielce, Poland.
³⁵ Department of Hematology, Medical University of Lodz, Lodz, Poland.
³⁶ Plasma Cell Dyscrasias Center, Department of Hematology, Faculty of Medicine, Jagiellonian University, Kraków, Poland.
³⁷ Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszów, Rzeszów, Poland.
³⁸ Servicio de Hematología Centro de Actividades Ambulatorias, Madrid, Spain.
³⁹ Department of Hematology, Transplantation and Internal Disease, Medical University of Warsaw, Warsaw, Poland.
⁴⁰ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴¹ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
⁴² CCU Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴³ Division of Population Oncology Cancer Control Research, BC Cancer, Vancouver, Bristish Columbia, Canada.
⁴⁴ Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁴⁵ Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, California.
⁴⁶ Latinos United for Cancer Health Advancement Initiative, University of California Davis Comprehensive Cancer Center, Sacramento, California.
⁴⁷ Community Engagement Program, Clinical and Translational Science Center, University of California Davis, Sacramento, California.
⁴⁸ Department of Hematology, University Hospital of Cracow, Cracow, Poland.
⁴⁹ Division of Epidemiology, Department of Quantitative Sciences, Mayo Clinic, Rochester, Minnesota.

^# Contributed equally.

PMID: 35700034
PMCID: PMC11375313
DOI: 10.1158/1055-9965.EPI-22-0043

Meta-Analysis

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

Angelica Macauda et al. Cancer Epidemiol Biomarkers Prev. 2022.

. 2022 Sep 2;31(9):1863-1866.

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

Authors

Affiliations

¹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Biology, University of Pisa, Pisa, Italy.
³ Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Greenville, South Carolina.
⁴ Division of Biostatistics, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
⁵ Department of Lymphoma - Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁶ Department of Hematology University Hospital Bydgoszcz, Bydgoszcz, Poland.
⁷ Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
⁸ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
⁹ Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
¹⁰ Department of Pathology, School of Medicine, University of Alabama, Birmingham, Alabama.
¹¹ Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
¹² Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
¹³ Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
¹⁴ Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
¹⁵ Division of Hematology and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
¹⁶ Department of Haematology and Bone Marrow Transplantation, SSM im. M. Kopernika, Torun, Poland.
¹⁷ Department of Hematology, Rydygier Hospital, Cracow, Poland.
¹⁸ Division of Hematology/Oncology, Department of Medicine, School of Medicine, Department of Pathology, School of Medicine, Susan and Henry Samueli College of Health Sciences, Chao Family Comprehensive Cancer Center, University of California at Irvine, California.
¹⁹ Department of Hematology and Internal Medicine, Semmelweis University, Budapest, Hungary.
²⁰ Department of Hematology, Military Institute of Medicine, Warsaw, Poland.
²¹ Biomedical Center, Faculty of Medicine, Charles University in Pilsen, Pilsen, Czech Republic.
²² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²³ Department of Hematology Specialist Hospital No. 1 in Bytom, Bytom, Poland.
²⁴ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
²⁵ Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
²⁶ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²⁷ Department of Hematology and Transplantology, Medical Univeristy of Gdańsk, Gdańsk, Poland.
²⁸ Department of Haematology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
²⁹ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
³⁰ Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Poland.
³¹ Genomic Oncology Area, GENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Granada, Spain.
³² Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.
³³ Department of Internal and Occupational Diseases, Medical University Wroclaw, Wroclaw, Poland.
³⁴ Hematology Clinic, Holycross Cancer Center, Kielce, Poland.
³⁵ Department of Hematology, Medical University of Lodz, Lodz, Poland.
³⁶ Plasma Cell Dyscrasias Center, Department of Hematology, Faculty of Medicine, Jagiellonian University, Kraków, Poland.
³⁷ Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszów, Rzeszów, Poland.
³⁸ Servicio de Hematología Centro de Actividades Ambulatorias, Madrid, Spain.
³⁹ Department of Hematology, Transplantation and Internal Disease, Medical University of Warsaw, Warsaw, Poland.
⁴⁰ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴¹ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
⁴² CCU Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴³ Division of Population Oncology Cancer Control Research, BC Cancer, Vancouver, Bristish Columbia, Canada.
⁴⁴ Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁴⁵ Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, California.
⁴⁶ Latinos United for Cancer Health Advancement Initiative, University of California Davis Comprehensive Cancer Center, Sacramento, California.
⁴⁷ Community Engagement Program, Clinical and Translational Science Center, University of California Davis, Sacramento, California.
⁴⁸ Department of Hematology, University Hospital of Cracow, Cracow, Poland.
⁴⁹ Division of Epidemiology, Department of Quantitative Sciences, Mayo Clinic, Rochester, Minnesota.

^# Contributed equally.

PMID: 35700034
PMCID: PMC11375313
DOI: 10.1158/1055-9965.EPI-22-0043

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.

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Conflict of interest statement

Conflict of interest: The authors declare no potential conflicts of interest.

Figures

**Figure 1.. Forest plot of 24-MM PRS and OS association.**
24-SNP MM-PRS was evaluated as a continuous variable, per standard deviation (SD). Meta-analysis using a fixed effects model was then used across all four datasets. HR=hazard ratio, 95% CI= 95% confidence interval.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical