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The insulin-like growth factor-1 (IGF-1) appears to be associated with several types of cancer, according to a new study published today in Cancer Research. This could eventually lead to broad-acting preventative interventions.

IGF-1 helps to support normal cell growth and development; processes which can lead to cancer if they become dysregulated. This study, a collaboration between the Cancer Epidemiology Unit (CEU) in NDPH, and the International Agency for Research on Cancer (IARC) in Lyon, is the largest and most comprehensive investigation on IGF-1 and cancer risk to date. For the first time, it assessed the link between raised IGF-1 and a broad range of cancers, including less common types where little is known about physiological risk factors.

The researchers analysed the serum IGF-1 levels in almost 400,000 blood samples held in the open-access UK Biobank resource, collected between 2006-2010. Using data records from the NHS up until 2016, the researchers could identify which of the sample donors went on to develop one of 30 different types of malignant cancers, within an average period of seven years. In total, 23,412 (5.9%) of the participants developed a malignant cancer. To test for an association between raised IGF-1 levels and cancer risk, the researchers adjusted the statistical analyses to correct for a range of other characteristics including age, sex, geographical region, ethnicity, physical activity, smoking, alcohol consumption and (for women) HRT use.

‘In this new study, we expanded the range of cancers investigated to include less common types that have rarely been investigated. This allowed us to identify a link between raised IGF-I levels and an increased risk for thyroid cancer in this UK cohort.’ says lead investigator, Dr Anika Knuppel of NDPH.

‘We are particularly confident about this result for thyroid cancer because we used very strict parameters to take into account chance results occurring in such a large dataset. Using slightly less strict parameters, we also identified a potential association between raised IGF-1 and increased risk for melanoma (skin cancer) and myeloma (cancer of the bone marrow). We intend to investigate this further.’ The results also confirmed previous studies which found a positive association between pre-diagnostic IGF-1 levels and colorectal, breast and prostate cancer, including a study led by Professor Tim Key at CEU and IARC.

Together, these results suggest that controlling IGF-1 through lifestyle interventions could be an effective preventative measure for a range of cancers. ‘There is some initial evidence, for instance, that higher dairy intakes can raise IGF-1 concentrations.’ says Dr Knuppel.

Some cancers, however, did not show a clear link between IGF-1 concentrations and risk. These included lung, bladder, pancreatic, endometrial and kidney cancer. ‘This is perhaps a little surprising, since IGF-1 is a growth promoting substance hence we would expect that it could promote growth for every type of cancer. It may be that these types of cancer are less sensitive to IGF-1, or that they are able to produce this hormone themselves locally.’ Dr Knuppel says.

Meanwhile, a few cancers (including liver and ovarian cancer) appeared to show the opposite trend, with increased risk associated with lower IGF-1 levels. ‘Because the follow-up time was fairly short, these results may have been caused by reverse causality, where a developing, undiagnosed condition was influencing IGF-1 levels at the time when the samples were taken’. says Dr Knuppel. ‘For instance, IGF-1 is made in the liver, hence an undiagnosed precancerous liver disease could have prevented the liver from producing normal levels of IGF-1.’

The study demonstrates the power of using population-level approaches to assess the extent to which risk factors apply across the entire cancer spectrum. ‘Particularly for rarer cancers, such as thyroid cancer, it is essential to use large, population-based studies such as these to identify potential risk factors.’ says Dr Knuppel. ‘The next stage of this work will be to test these associations in further cohorts, including from different countries.’

This work was supported by Cancer Research UK, UK Medical Research Council, Wellcome, and a Nuffield Department of Population Health Early Career Research Fellowship grant. The researchers thank all participants, researchers and support staff who made the study possible.