TY - JOUR
T1 - Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
AU - Macauda, Angelica
AU - Clay-Gilmour, Alyssa
AU - Hielscher, Thomas
AU - Hildebrandt, Michelle At
AU - Kruszewski, Marcin
AU - Orlowski, Robert Z
AU - Kumar, Shaji K
AU - Ziv, Elad
AU - Orciuolo, Enrico
AU - Brown, Elizabeth E
AU - Försti, Asta
AU - Waller, Rosalie G
AU - Machiela, Mitchell J
AU - Chanock, Stephen J
AU - Camp, Nicola J
AU - Rymko, Marcin
AU - Raźny, Malgorzata
AU - Cozen, Wendy
AU - Varkonyi, Judit
AU - Piredda, Chiara
AU - Pelosini, Matteo
AU - Belachew, Alem A
AU - Subocz, Edyta
AU - Hemminki, Kari
AU - Rybicka-Ramos, Malwina
AU - Giles, Graham G
AU - Milne, Roger L
AU - Hofmann, Jonathan N
AU - Zaucha, Jan Maciej
AU - Vangsted, Annette Juul
AU - Goldschmidt, Hartmut
AU - Rajkumar, S Vincent
AU - Tomczak, Waldemar
AU - Sainz, Juan
AU - Butrym, Aleksandra
AU - Watek, Marzena
AU - Iskierka-Jazdzewska, Elzbieta
AU - Buda, Gabriele
AU - Robinson, Dennis P
AU - Jurczyszyn, Artur
AU - Dudzinski, Marek
AU - Martinez-Lopez, Joaquin
AU - Sinnwell, Jason P
AU - Slager, Susan L
AU - Jamroziak, Krzysztof
AU - Reis, Rui Manuel
AU - Weinhold, Niels
AU - Bhatti, Parveen
AU - Carvajal-Carmona, Luis G
AU - Zawirska, Daria
AU - Norman, Aaron D
AU - Mazur, Grzegorz
AU - Berndt, Sonja I
AU - Campa, Daniele
AU - Vachon, Celine M
AU - Canzian, Federico
PY - 2022/9/2
Y1 - 2022/9/2
N2 - 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.
AB - 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.
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study/methods
KW - Humans
KW - Multiple Myeloma/genetics
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1158/1055-9965.EPI-22-0043
DO - 10.1158/1055-9965.EPI-22-0043
M3 - Journal article
C2 - 35700034
SN - 1055-9965
VL - 31
SP - 1863
EP - 1866
JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
IS - 9
ER -