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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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Despite reporting lower levels of alcohol consumption, people with lower socio-economic status (SES) experience greater alcohol-related harm. Whether differential biases in the measurement of alcohol use could explain this apparent paradox is unknown. Using alcohol biomarkers to account for measurement error, we examined whether differential exposure to alcohol could explain the socio-economic differences in alcohol mortality., Methods: Participants from eight representative health surveys (n = 52 164, mean age 47.7 years) were linked to mortality data and followed up until December 2016. The primary outcome was alcohol-attributable mortality. We used income and education as proxies for SES. Exposures include self-reported alcohol use and four alcohol biomarkers [serum gamma-glutamyl transferase (available in all surveys), carbohydrate-deficient transferrin, alanine aminotransferase and aspartate aminotransferase (available in subsamples)]. We used shared frailty Cox proportional hazards to account for survey heterogeneity., Results: During a mean follow-up of 20.3 years, totalling 1 056 844 person-years, there were 828 alcohol-attributable deaths. Lower SES was associated with higher alcohol mortality despite reporting lower alcohol use. Alcohol biomarkers were associated with alcohol mortality and improved the predictive ability when used in conjunction with self-reported alcohol use. Alcohol biomarkers explained a very small fraction of the socio-economic differences in alcohol mortality, since hazard ratios either slightly attenuated (percent attenuation range 1.0-12.1%) or increased., Conclusions: Using alcohol biomarkers in addition to self-reported alcohol use did not explain the socio-economic differences in alcohol mortality. Differential bias in the measurement of alcohol use is not a likely explanation for the alcohol-harm paradox., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)