Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
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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 Maciej, Vangsted Annette Juul, Goldschmidt Hartmut, Rajkumar S Vincent, Tomczak Waldemar, Sainz Juan, Butrym Aleksandra, Watek Marzena, Iskierka-Jazdzewska Elżbieta, Buda Gabriele, Robinson Dennis P, Jurczyszyn Artur, Dudziński 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
Аннотация
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.