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Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis.

Authors :
Watts, Eleanor L
Perez-Cornago, Aurora
Fensom, Georgina K
Smith-Byrne, Karl
Noor, Urwah
Andrews, Colm D
Gunter, Marc J
Holmes, Michael V
Martin, Richard M
Tsilidis, Konstantinos K
Albanes, Demetrius
Barricarte, Aurelio
Bueno-de-Mesquita, H Bas
Cohn, Barbara A
Deschasaux-Tanguy, Melanie
Dimou, Niki L
Ferrucci, Luigi
Flicker, Leon
Freedman, Neal D
Giles, Graham G
Source :
International Journal of Epidemiology; Feb2023, Vol. 52 Issue 1, p71-86, 16p
Publication Year :
2023

Abstract

Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03005771
Volume :
52
Issue :
1
Database :
Complementary Index
Journal :
International Journal of Epidemiology
Publication Type :
Academic Journal
Accession number :
161877896
Full Text :
https://doi.org/10.1093/ije/dyac124