Dataset Information

Circulating Insulin-Like Growth Factor-1 and Risk of Total and 19 Site-Specific Cancers: Cohort Study Analyses from the UK Biobank.

ABSTRACT:

Background

Insulin-like growth factor-1 (IGF-1) has been implicated in several malignancies, but few studies have examined multiple cancers simultaneously. We sought to conduct systematic assessments of the association between IGF-1 and cancer risk.

Methods

We conducted a prospective analysis between IGF-1 and incident total and 19 site-specific cancers among 412,645 individuals enrolled in the UK Biobank with follow-up to 2016. IGF-1 was measured using blood samples provided at the baseline examination. HR and 95% confidence interval (CI) were calculated with multivariable-adjusted Cox models with IGF-1 modeled both in sex-specific quintiles and continuously.

Results

Participants were followed for a median of 7.2 years. We observed positive associations between circulating IGF-1 and overall cancer risk for both men (HR = 1.03 per 5-nmol/L increment in IGF-1; 95% CI, 1.01-1.06) and women (HR = 1.03; 95% CI, 1.01-1.06). For specific sites, we observed positive associations for breast (HR = 1.10; 95% CI, 1.07-1.14), prostate (1.09; 95% CI, 1.05-1.12), colorectum (1.07; 95% CI, 1.02-1.11), melanoma (1.08; 95% CI, 1.01-1.15), kidney (1.10; 95% CI, 1.00-1.20), and thyroid (1.22; 95% CI, 1.05-1.42) and inverse associations for lung (0.91; 95% CI, 0.86-0.96), ovaries (0.86; 95% CI, 0.77-0.95), head and neck (0.90; 95% CI, 0.82-0.99), and liver (0.32; 95% CI, 0.26-0.38). The inverse association between IGF-1 and lung cancer was observed only in ever-smokers (HR_ever-smoker = 0.88 vs. HR_never-smoker = 1.14; P_interaction = 0.0005). Analyses comparing extreme quintiles were consistent.

Conclusions

IGF-1 is modestly associated with increased risk of total cancer in both men and women but demonstrated divergent associations for site-specific cancers.

Impact

Our study suggests that IGF-1 could serve as a target for cancer prevention or treatment.

SUBMITTER: Qian F

PROVIDER: S-EPMC7642199 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features.MethodsThis prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest - dementia, stroke, and Parkinson's disease (PD) - at enrollment (2006-2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014.ResultsDuring a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose-response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (β = 2.98 × 10-4, P < 0.001) and hippocampus (β = 3.37 × 10-4, P = 0.002) and smaller white matter hyperintensity (β = -3.12 × 10-3, P < 0.001).ConclusionsApart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.