The growth hormone insulin-like growth factor-1 (IGF-1) is likely to play a role in the development of breast cancer, according to new research published in Annals of Oncology today.
IGF-1 is already known to encourage the growth and proliferation of cancer cells. Now, two analyses have shown an association between higher levels of IGF-1 circulating in the blood and the development of breast cancer, and that IGF-1 is likely to be a cause of breast cancer.
Researchers from the Cancer Epidemiology Unit (CEU) in NDPH, and the International Agency for Research on Cancer (IARC) in Lyon carried out complementary studies to investigate the role of IGF-1 in breast cancer development. The team at CEU, led by Professor Tim Key, looked at the associations between levels of IGF-1 in the blood and the chances of the disease developing in 206,263 women enrolled in UK Biobank. They found that women with IGF-1 concentrations in the top 20% had 1.24-fold increased chance of developing breast cancer compared to those in the bottom 20%, after adjustments for various factors that could affect the results, such as age, body mass index, health behaviours, educational level and concentrations of other hormones and proteins in the blood.
The research group at IARC used Mendelian randomisation to analyse data from 265 variants of genes (single nucleotide polymorphisms or “SNPs”) known to be associated with IGF-1 concentrations in 122,977 women with breast cancer and 105,974 women without cancer. Results showed that for every additional genetically predicted 5 nmol/L of IGF-1, the risk of breast cancer increased by 1.05. When the researchers looked at oestrogen receptor positive (ER+) and negative (ER-) breast cancers separately they found that IGF-1 was only associated with an increased risk of ER+ breast cancer.
Mendelian randomisation uses complex statistical analysis of data from large population studies to provide evidence for cause and effect, rather than mere association. Randomly inherited genetic variations that alter levels of IGF-1 and IGFBP-3 mimic the effect of a randomised trial and are unaffected by the disease process, so the researchers were able to use them to see whether people with a different genetic make-up had a different risk of breast cancer.
Dr Anika Knüppel, a nutritional epidemiologist at CEU, said: “The association between IGF-1 and breast cancer was first investigated in the 1980s and our findings are in line with various studies since then. But clarifying the direction of the association using Mendelian randomisation in our study leads the way for research into how the IGF-1 pathway can be harnessed in breast cancer prevention.”