Sistema de Salut de Catalunya
Institut Català de la Salut
[Sánchez-Maldonado JM, Cabrera-Serrano AJ] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain. [Chattopadhyay S] Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany. [Campa D] Department of Biology, University of Pisa, Pisa, Italy. [Garrido MDP] Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Macauda A] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jerez A] Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-05-05T12:53:29Z
2023-05-05T12:53:29Z
2023-03-23
Genetic variants; Multiple myeloma; Obesity
Variantes genéticas; Mieloma múltiple; Obesidad
Variants genètiques; Mieloma múltiple; Obesitat
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.
This work was supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI17/02256 and PI20/01845), from the Consejería de Salud y Familia de la Junta de Andalucía (PY20/01282) and from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS (01ZX1309)).
Article
Published version
English
Mieloma múltiple - Aspectes genètics; Obesitat - Complicacions; DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Hemorrhagic Disorders::Hemostatic Disorders::Multiple Myeloma; DISEASES::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight::Obesity; PHENOMENA AND PROCESSES::Genetic Phenomena::Genotype::Genetic Predisposition to Disease; ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos hemorrágicos::trastornos hemostáticos::mieloma múltiple; ENFERMEDADES::afecciones patológicas, signos y síntomas::signos y síntomas::peso corporal::sobrepeso::obesidad; FENÓMENOS Y PROCESOS::fenómenos genéticos::genotipo::predisposición genética a la enfermedad
MDPI
International Journal of Molecular Sciences;24(7)
https://doi.org/10.3390/ijms24076029
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
