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A study of almost 400,000 British participants has identified a new link between raised levels of the growth factor IGF-1 and increased thyroid cancer risk and has confirmed associations with breast, prostate and colorectal cancer.

IGF-1 (insulin-like growth factor-1) helps to support normal cell growth and development; processes which can lead to cancer if they become dysregulated. This study, published in the journal Cancer Research, is a collaboration between the Cancer Epidemiology Unit (CEU) in Nuffield Department of Population Health, and the International Agency for Research on Cancer (IARC) in Lyon. This research is the largest and most comprehensive investigation on IGF-1 and cancer risk to date.

The researchers analysed the serum IGF-1 levels in almost 400,000 blood samples from the UK Biobank. Using NHS data records, 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) hormone replacement therapy use.

Higher IGF-1 concentration was associated with increased risks of thyroid cancer, in addition to confirming previous studies which found a positive association between pre-diagnostic IGF-1 levels and colorectal, breast and prostate cancer. 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 that other risk factors such as smoking are dominant - Dr Anika Knuppel, lead investigator

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. 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. - Dr Knuppel

Together, these results suggest that reducing levels of the growth hormone IGF-1 through lifestyle interventions might decrease risk for a range of cancers, a strategy that requires further research.

 

There is some initial evidence, for instance, that higher dairy intakes can raise IGF-1 concentrations. The next stage of this work will be to test these associations in further cohorts, including from different countries. 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. - Dr Knuppel

This work was supported by Cancer Research UK, UK Medical Research Council, the Wellcome Trust, 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.

See the Nuffield Department of Population Health website for the full story.