Circulating levels of insulin‐like growth factor I ( <scp>IGF</scp> ‐I) and risk of multiple myeloma: An observational and Mendelian randomisation study

Evidence for an association between insulin-like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF-I concentrations and risk of MM by combining baseline serological data among UK Biobank participants (n = 444 187; 732 incident MM) with a two-sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF-I and IGF-binding protein 3 (IGFBP-3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF-I level was positively associated with MM risk Hazard ratio-HR-per one standard deviation-SD-increase (HR<sub>1-SD</sub> = 1.11, 95% confidence interval [CI]: 1.01-1.22; p-value = 0.03), especially closer to diagnosis. Genetically inferred IGF-I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05-1.54) but not with any other LNs. Genetically inferred IGFBP-3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF-I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR<sub>1-SD in obese male</sub> = 1.36, 95% CI: 1.14-1.61). Our serological and MR analyses suggest a contributing role of IGF-I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex-specific adiposity.

Institutions

Publication Details

Journal
British Journal of Haematology
Published
2026-03-23
DOI
https://doi.org/10.1111/bjh.70444
Primary Topic
Growth Hormone and Insulin-like Growth Factors
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Circulating levels of insulin‐like growth factor I ( IGF ‐I) and risk of multiple myeloma: An observational and Mendelian randomisation study

British Journal of Haematology
Growth Hormone and Insulin-like Growth Factors
article

Circulating levels of insulin‐like growth factor I ( IGF ‐I) and risk of multiple myeloma: An observational and Mendelian randomisation study

article en

Abstract

Evidence for an association between insulin-like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF-I concentrations and risk of MM by combining baseline serological data among UK Biobank participants (n = 444 187; 732 incident MM) with a two-sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF-I and IGF-binding protein 3 (IGFBP-3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF-I level was positively associated with MM risk Hazard ratio-HR-per one standard deviation-SD-increase (HR<sub>1-SD</sub> = 1.11, 95% confidence interval [CI]: 1.01-1.22; p-value = 0.03), especially closer to diagnosis. Genetically inferred IGF-I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05-1.54) but not with any other LNs. Genetically inferred IGFBP-3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF-I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR<sub>1-SD in obese male</sub> = 1.36, 95% CI: 1.14-1.61). Our serological and MR analyses suggest a contributing role of IGF-I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex-specific adiposity.

British Journal of Haematology
Délégation Paris 5 (FR), University of Copenhagen (DK), University of Iowa (US), Brigham and Women's Hospital (US), American Cancer Society (US), BC Cancer Agency (CA), National Institutes of Health (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Karolinska University Hospital (SE), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), University of British Columbia (CA), Inserm (FR), University of South Carolina (US), The University of Melbourne (AU), University of Cagliari (IT), Universidad de Granada (ES), Université de Bourgogne (FR), University of California, San Francisco (US), Utrecht University (NL), Cancer Council Victoria (AU), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), University of California, Irvine (US), Université Paris Cité (FR), Cornell University (US), Manchester Academic Health Science Centre (GB), Huntsman Cancer Institute (US), Copenhagen University Hospital (DK), Rigshospitalet (DK), Karolinska Institutet (SE), UNSW Sydney (AU), University of Alabama at Birmingham (US), Kettering University (US), Sorbonne Paris Cité (FR), University of California, Irvine Medical Center (US), Hospices Civils de Lyon (FR), Institut Català d'Oncologia (ES), Hôpital Lyon Sud (FR), Instituto de Investigación Biosanitaria de Granada (ES), Conseil Régional de Basse-Normandie (FR), Monash Health (AU), Institut Bergonié (FR), Institute of Population and Public Health (CA), Interactions, Corpus, Apprentissages, Représentations (FR), National Cancer Institute (US), Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (ES), Mayo Clinic in Florida (US), Danish Cancer Society (DK), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), UCSF Helen Diller Family Comprehensive Cancer Center (US), Centre international de recherche sur le cancer (FR), Centre de Recherche Épidémiologie et Statistique (FR), University of York (GB), Monash University (AU), New York University (US), Universitat de Barcelona (ES)
Good health and well-being
Openalex Percentile: Top 12%
Growth Hormone and Insulin-like Growth Factors
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.