| Title: | Circulating levels of insulin-like growth factor I (IGF-I) and risk of multiple myeloma: An observational and Mendelian randomisation study |
| Journal: | British Journal of Haematology |
| Published: | 23 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41873017/ |
| DOI: | https://doi.org/10.1111/bjh.70444 |
Publication 18227
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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 (HR1-SD = 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 (HR1-SD in obese male = 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.</p>
57 Authors
- Yolanda Benavente
- Sara Hermosa
- Nikos Papadimitriou
- Alyssa Clay-Gilmour
- Elizabeth E. Brown
- Jonathan N. Hofmann
- Nathaniel Rothman
- Qing Lan
- Sonja I. Berndt
- Demetrius Albanes
- Mark Purdue
- Mitchell J. Machiela
- Stephen J. Chanock
- Parveen Bhatti
- Wendy Cozen
- Aaron Norman
- Susan L. Slager
- James R. Cerhan
- Vincent Rajkumar
- Shaji K. Kumar
- Celine M. Vachon
- Anne J. Novak
- Thomas M. Habermann
- Brian K. Link
- Gilles Salles
- Herve Ghesquieres
- Paige M. Bracci
- Elizabeth Holly
- Rosalie G. Griffin
- Michelle A. T. Hildebrandt
- Roel C. H. Vermeulen
- P. Martijn Kolijn
- Henrik Hjalgrim
- Karin Ekström Smedby
- Harindra Jayasekara
- Simon Cheah
- Alain Monnereau
- Yu Chen
- Alan Arslan
- Yawei Zhang
- Nicola J. Camp
- Douglas W. Sborov
- Afaf E. G. Osman
- Elad Ziv
- Immaculata De Vivo
- Vijai Joseph
- Lauren R. Teras
- Alpa V. Patel
- Eleanor Kane
- Claire M. Vajdic
- Adrien Guilloteau
- Pierluigi Cocco
- Laia Alemany
- Juan Sainz
- James McKay
- Brenda M. Birmann
- Delphine Casabonne
1 Application
| Application ID | Title |
|---|---|
| 52433 | Prospective study of risk factors for multiple myeloma and its precursors in the context of the UK Biobank Cohort study |
Enabling scientific discoveries that improve human health