Assessing the effect of obesity-related traits on multiple myeloma using a Mendelian randomisation approach

Went, Molly; Sud, Amit; Law, Philip; Johnson, David C.; Weinhold, Niels; Försti, Asta; Duin, Mark van; Mitchell, Jonathan S.; Chen, B.; Kuiper, Rowan; Stephens, Owen; Bertsch, Uta; Campo, C; Einsele, Hermann; Gregory, Walter M.; Henrion, Marc; Hillengaß, Jens; Hoffmann, Per; Jackson, Graham; Lenive, Oleg; Nickel, Jolanta; Nöthen, Markus M.; Filho, Miguel Inácio da Silva; Thomsen, Hauke; Walker, Brian A.; Broyl, Annemiek; Davies, Faith E.; Langer, Christian; Hansson, Markus; Kaiser, Martin; Sonneveld, Pieter; Goldschmidt, Hartmut; Hemminki, Kari; Nilsson, Björn; Morgan, Gareth J.; Houlston, Richard S.

doi:10.1038/bcj.2017.48

Cited by 10 publications

(8 citation statements)

References 15 publications

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“…This two-stage case–control association study showed that there is no significant association between GWAS-identified variants for obesity and MM risk. These findings were in agreement with a recent study that, using a Mendelian randomization strategy, demonstrated that SNPs associated with BMI, hip and waist circumference, waist-to-hip ratio, and childhood obesity were not involved in the modulation of MM risk [ 14 ]. In line with these negative findings, we neither found a positive correlation between obesity-related SNPs and cQTL data, serum inflammatory protein levels, steroid hormone levels, nor absolute numbers of blood-derived cell populations in the Human Functional Genomics Project (HFGP) cohort, which reinforced the hypothesis suggesting no effect of GWAS-identified SNPs for obesity in modulating MM risk.…”

Section: Discussionsupporting

confidence: 93%

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

Sánchez-Maldonado

Cabrera-Serrano

Chattopadhyay

et al. 2023

IJMS

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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.

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Section: Discussionsupporting

confidence: 93%

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

Sánchez-Maldonado

Cabrera-Serrano

Chattopadhyay

et al. 2023

IJMS

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“…In contrast, we could not find an association for leukaemia that has previously been reported to be associated with central adiposity 49 . For multiple myeloma, while a recent Mendelian randomisation study reported a non-significant ( p = 0.06) reverse association of the BMI-adjusted WC 50 , we found a positive association in female ( P trend = 0.003). Given the largely unknown etiology and the heterogeneous entity of these malignancies, further studies are warranted to clarify their associations with central adiposity.…”

Section: Discussioncontrasting

confidence: 75%

Waist circumference and risk of 23 site-specific cancers: a population-based cohort study of Korean adults

et al. 2018

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Background Large waist circumference (WC) is a risk factor for several site-specific cancers, but a large-scale systematic investigation across all common cancers adjusted for potential confounders has not been conducted. This study aimed to evaluate the possible links between WC and common cancers. Methods We prospectively examined the association between WC and the risk of cancers in a 7-year cohort study of nearly 22.9 million Korean adults. Using the claims database merged with the national health check-up data, we fitted proportional hazard models to investigate associations between WC and 23 of the most common cancers, with adjustment for potential confounders, including body mass index (BMI). We also evaluated the modification of BMI on the relationships between WC and the incidence of cancer. Results A total of 769,871 cancer cases were identified. WC was positively associated with 18 of 23 cancers, and the effects varied substantially by site in each sex. The modification of BMI on the WC-cancer association also varied across the cancer site; in most cases it mitigated the association. For cancers of the oral cavity, larynx, oesophagus, lung, and premenopausal breast, the BMI adjustment reversed the association toward being positive (all P trend < 0.001). Conclusions Central obesity, independent of general obesity, was associated with the risk of several cancers. The heterogeneity in the mediating effects of BMI suggests that different mechanisms are associated with different cancer sites. Based upon these findings, active strategies to monitor and prevent central obesity should be implemented.

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“…Mendelian randomization studies have shown contradictory results. Although the two prior studies have not shown a significant correlation between obesity/adiposity and risk of MM [ 114 , 115 ], a recent study revealed a possible causal relationship between MM and greater genetically instrumented unfavorable adiposity according to single nucleotide polymorphisms [ 116 ].…”

Section: Metabolic Syndromementioning

confidence: 99%

Metabolic Disorders in Multiple Myeloma

Gavriatopoulou

Paschou

Ntanasis‐Stathopoulos

et al. 2021

IJMS

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Multiple myeloma (MM) is the second most common hematological malignancy and is attributed to monoclonal proliferation of plasma cells in the bone marrow. Cancer cells including myeloma cells deregulate metabolic pathways to ensure proliferation, growth, survival and avoid immune surveillance, with glycolysis and glutaminolysis being the most identified procedures involved. These disorders are considered a hallmark of cancer and the alterations performed ensure that enough energy is available for rapid cell proliferation. An association between metabolic syndrome, inflammatory cytokinesand incidence of MM has been also described, while the use of metformin and statins has been identified as a positive prognostic factor for the disease course. In this review, we aim to present the metabolic disorders that occur in multiple myeloma, the potential defects on the immune system and the potential advantage of targeting the dysregulated pathways in order to enhance antitumor therapeutics.

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Assessing the effect of obesity-related traits on multiple myeloma using a Mendelian randomisation approach

Cited by 10 publications

References 15 publications

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

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

Waist circumference and risk of 23 site-specific cancers: a population-based cohort study of Korean adults

Metabolic Disorders in Multiple Myeloma

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