GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis

被引：1

作者：

Sanchez-Maldonado, Jose Manuel ^{[1
]}

Cabrera-Serrano, Antonio Jose ^{[1
]}

Chattopadhyay, Subhayan ^{[2
,3
,4
]}

Campa, Daniele ^{[5
]}

Garrido, Maria del Pilar ^{[6
]}

Macauda, Angelica ^{[7
]}

Ter Horst, Rob ^{[8
,9
]}

Jerez, Andres ^{[10
]}

Netea, Mihai G. G. ^{[8
,9
,11
]}

Li, Yang ^{[8
,9
,12
,13
,14
]}

Hemminki, Kari ^{[2
,15
,16
,17
]}

Canzian, Federico ^{[7
]}

Foersti, Asta ^{[3
,4
]}

Sainz, Juan ^{[1
,18
]}

机构：

[1] Pfizer Univ Granada Andalusian Reg Govt, Ctr Genom & Oncol Res, Genom Oncol Area, GENYO, Granada 18016, Spain

[2] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany

[3] German Canc Consortium DKTK, Div Pediat Neurooncol, German Canc Res Ctr DKFZ, D-69120 Heidelberg, Germany

[4] Hopp Childrens Canc Ctr KiTZ, D-69120 Heidelberg, Germany

[5] Univ Pisa, Dept Biol, I-56126 Pisa, Italy

[6] Virgen Las Nieves Univ Hosp, Hematol Dept, Granada 18012, Spain

[7] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

[8] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[9] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[10] Univ Hosp Vall Hebron, Vall Hebron Inst Oncol VHIO, Dept Hematol, Expt Hematol Unit, Barcelona 08035, Spain

[11] Univ Bonn, Life & Med Sci Inst LIMES, Dept Immunol & Metab, D-53115 Bonn, Germany

[12] Ctr Individualised Infect Med CiiM, D-30625 Hannover, Germany

[13] TWINCORE, Joint Ventures Helmholtz Ctr Infect Res HZI, D-30625 Hannover, Germany

[14] Hannover Med Sch MHH, D-30625 Hannover, Germany

[15] German Canc Res Ctr, Germany Div Canc Epidemiol, D-69120 Heidelberg, Germany

[16] Charles Univ Prague, Fac Med, Plzen 30605, Czech Republic

[17] Charles Univ Prague, Biomed Ctr Pilsen, Plzen 30605, Czech Republic

[18] Univ Granada, Dept Biochem & Mol Biol 1, Granada 18071, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 07期

关键词：

multiple myeloma; obesity; genetic variants; susceptibility; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; NON-HODGKINS-LYMPHOMA; COMMON VARIANTS; GENETIC-LOCI; LIFE; FAT; INDIVIDUALS; OVERWEIGHT; ADIPOSITY;

D O I：

10.3390/ijms24076029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 POC5(rs2112347G) and ADCY3(rs11676272G) 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.

引用

页数：10

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