Figure 1.

Risks of overall, aggressive* and early-onset† prostate cancer by study-specific fifths of biomarker concentrations (observational only) and 1 SD increment (observational and Mendelian randomization). Estimates are from logistic regression conditioned on the matching variables and adjusted for age, BMI, height, alcohol intake, smoking status, marital status, education status, racial/ethnic group and diabetes status. The position of each square indicates the magnitude of the odds ratio, and the area of the square is proportional to the inverse of the variance of the log odds ratio. The length of the horizontal line through the square indicates the 95% confidence interval. MR risk estimates are estimated using the inverse-variance weighted method for the full instrument methods and the Wald ratio in the cis-SNP analyses. P_trend represents 1-SD increase in biomarker concentration. *Aggressive cancer defined as Gleason grade 8+, or prostate cancer death, or metastases or PSA >100 ng/mL. †Early-onset defined as diagnosed ≤55 years. BMI, body mass index; CI, confidence interval; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; OR, odds ratio; PSA, prostate-specific antigen; SD, standard deviation; MR, Mendelian randomization; SNP, single nucleotide polymorphism