Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank

Abstract

Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable-adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias.Higher IGF-I concentration was associated with increased risks of thyroid cancer (hazard ratio per 5 nmol/l higher concentration 1.18; 95% confidence interval 1.01-1.37) in addition to colorectal (1.08; 1.03-1.13), breast (1.11; 1.07-1.15), and prostate cancer (1.08; 1.05-1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and cannot exclude the possibility that the observed associations may be influenced by reverse causality bias. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma, did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development.

Prospective analyses of testosterone and sex hormone‐binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank

“…Adjustment covariates were defined a priori based on previous analyses of UK Biobank data. 33 Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated per increment in each hormone, using the trend across the medians of the quartiles to estimate the linear trends. The increments were per 50 pmol/L, per 5 nmol/L and 10 nmol/L for free testosterone, total testosterone and SHBG, respectively for men and per 10 pmol/L, per 0.5 nmol/L and 25 nmol/L, respectively for postmenopausal women, and were chosen based on the sex-specific hormone SDs).…”

Circulating insulin-like growth factor-I and risk of 25 common conditions: outcome-wide analyses in the UK Biobank Study

“…kidney stones, enlarged prostate 4 ), respiratory disease, sleep apnoea, and some cancers. 5,6 Higher IGF-I concentrations in adults without acromegaly have been shown to also be associated with increased risks of several cancers, 7 but corresponding evidence for noncancer outcomes is inconsistent and/or limited to cross-sectional design. Although some of the available prospective observational and genetic evidence suggests that higher IGF-I levels might be positively associated with type 2 diabetes, 8,9 ischaemic heart disease (IHD), [9][10][11] hip and knee osteoarthritis, 12 enlarged prostate, 13 and colon adenomas, 14,15 some studies also reported null, [16][17][18][19][20][21][22][23][24] and inverse 25 associations for these outcomes.…”

Free testosterone and malignant melanoma risk in men: prospective analyses of testosterone and SHBG with 19 cancers in men and postmenopausal women UK Biobank

“…For postmenopausal women, we additionally adjusted for past HRT use (never, ever), past oral contraceptive pill use (never, ever), parity and age at first birth (nulliparous; 1-2, <25; 1-2, 25-29; 1-2, ≥30; 1-2, unknown; ≥3, <25; ≥3, 25-29; ≥3, ≥30 years, unknown (16.0%)), age at menarche (<12, 12-13,≥14 years, unknown (2.9%)), and age at menopause (<45, 45-49, 50-54, ≥ 55 years, unknown (14.9%)). Adjustment covariates were defined a priori based on previous analyses of UK Biobank data(32).…”