TY  - JOUR
AU  - Sánchez-Maldonado, José Manuel
AU  - Cabrera-Serrano, Antonio José
AU  - Chattopadhyay, Subhayan
AU  - Campa, Daniele
AU  - Garrido, María Del Pilar
AU  - Macauda, Angelica
AU  - Ter Horst, Rob
AU  - Jerez, Andrés
AU  - Netea, Mihai G
AU  - Li, Yang
AU  - Hemminki, Kari
AU  - Canzian, Federico
AU  - Försti, Asta
AU  - Sainz, Juan
TI  - GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis.
JO  - International journal of molecular sciences
VL  - 24
IS  - 7
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2023-00754
SP  - 6029
PY  - 2023
AB  - Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.
KW  - Humans
KW  - Genome-Wide Association Study: methods
KW  - Genetic Predisposition to Disease
KW  - Multiple Myeloma: genetics
KW  - Risk Factors
KW  - Obesity: complications
KW  - Obesity: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Carrier Proteins
KW  - genetic variants (Other)
KW  - multiple myeloma (Other)
KW  - obesity (Other)
KW  - susceptibility (Other)
KW  - POC5 protein, human (NLM Chemicals)
KW  - Carrier Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37047000
C2  - pmc:PMC10094344
DO  - DOI:10.3390/ijms24076029
UR  - https://inrepo02.dkfz.de/record/275431
ER  -