Circulating insulin-like growth factor-I (IGF-I) concentrations and risk of 30 cancers: prospective analyses in UK Biobank


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Anika Knuppel1, Georgina K. Fensom, Eleanor L. Watts, Marc J. Gunter, Neil Murphy, Keren Papier, Aurora Perez-Cornago, Julie A. Schmidt, Karl Smith Byrne, Ruth C. Travis, Timothy J. Key
1Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford

Abstract

Background

Insulin-like growth factor-I (IGF-I) is suggested to support cancer cell growth and proliferation. Pre-diagnostic circulating IGF-I concentrations have been shown to be positively associated with risk for breast cancer, prostate cancer and colorectal cancer but evidence for less common cancer sites 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.

Method

We analysed data from 394,388 cancer-free participants (52% women). IGF-I was measured in serum collected at baseline and for a subsample of 14,149 participants again in repeat samples collected during follow-up. Cancer diagnosis and death due to cancer during follow-up were determined using data-linkage with cancer and death registries. Multivariable-adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using the repeated measurements to correct estimates for regression dilution.

Results

After a mean follow-up of 6.9 years, 23,412 participants were diagnosed with a malignant cancer. 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. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer and esophageal squamous cell carcinoma did not survive correction for multiple testing.

Conclusion

The results from this outcome-wide analysis are consistent with a positive association of IGF-I with cancers at several sites. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development.

Impact statement

To our knowledge, this is the most comprehensive examination of the associations between circulating IGF-I concentrations and cancer risk to date.