Document Type

Article

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.

Digital Object Identifier (DOI)

https://doi.org/10.1111/bjh.70444

Rights

© 2026 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

APA Citation

Benavente, Y., Hermosa, S., Papadimitriou, N., Clay‐Gilmour, A., Brown, E. E., Hofmann, J. N., Rothman, N., Lan, Q., Berndt, S. I., Albanes, D., Purdue, M., Machiela, M. J., Chanock, S. J., Bhatti, P., Cozen, W., Norman, A., Slager, S. L., Cerhan, J. R., Rajkumar, V., & Kumar, S. K. (2026). 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, 208(6), 1942–1953. https://doi.org/10.1111/bjh.70444

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