Growth Hormone Found to Play a Role in Breast Cancer Development

A growth hormone known as insulin-like growth factor-1 (IGF-1) has been found to play a role in the development of breast cancer, according to a new article published in Annals of Oncology.

Previous research has indicated that IGF-1 encourages the growth and proliferation of cancer cells. However, the new analyses using data from individuals enrolled in the UK Biobank study have shown an association between higher levels of IGF-1 circulating in the blood and the development of breast cancer. Additionally, researchers have found for the first time that IGF-1 may be the cause of the disease.

A research team from the International Agency for Research on Cancer (IARC) and the Cancer Epidemiology Unit at the University of Oxford carried out 2 complementary studies to investigate the role of IGF-1 in breast cancer development.

The first examined the associations between levels of IGF-1 in the blood and the chances of the disease developing in approximately 206,263 women.

The second study used a technique known as Mendelian randomization to analyze data from 265 variants of genes, or single nucleotide polymorphisms (SNPs), which are associated with IGF-1 concentrations, in 122,977 cases of breast cancer and 105,974 women without cancer. In this analysis, the researchers also examined 4 SNPs for insulin-like growth factor-binding protein-3 (IGFBP-3), which modulates the availability of IGF-1.

After an average of 7 years of follow-up, 4360 cases of breast cancer occurred. Among the 206,263 women included in the observational analysis, IGF-1 levels ranged between an average of approximately 14 nanomoles per liter (nmol/L) of blood among participants with levels in the lowest 20% and 29 nmol/L in the top 20%.

Researchers found in the observational study that women with IGF-1 concentrations in the top 20% had a 1.24 times greater risk of developing breast cancer compared with those in the bottom 20%, after adjusting for age, physical activity, body mass index, alcohol, smoking, and other factors. For every 1000 women in the study who had the lowest IGF-1 concentrations, 21 were diagnosed with breast cancer during the study period, while 26 were diagnosed among those who had the highest concentration.

Every additional 5 nmol/L of IGF-1 concentrations were associated with a 1.11-fold increased risk. The results were consistent for both pre- and post-menopausal women.

The Mendelian randomization study found that for every additional genetically predicted 5 nmol/L of IGF-1, the risk of breast cancer increased by 1.05. However, when researchers examined estrogen receptor (ER)-positive and ER-negative breast cancers separately, IGF-1 was only associated with an increased risk of ER-positive breast cancer. For every additional 5 nmol/L of IGF-1, there was a 1.06-fold increased risk of ER-positive breast cancer. No association was found for IGFBP-3 concentrations and breast cancer risk.

Researchers found that higher levels of IGF-1 circulating in the blood were related to higher breast cancer risk, meaning that the results support a probable causal role of the IGF pathway in breast cancer development.

In a press release, Marc Gunter, MD, scientist and head of the nutrition and metabolism section at IARC, said: "To our knowledge, this is largest single study and the first Mendelian randomization study to examine the relationship between IGF-1 and breast cancer. Importantly, our Mendelian randomization analyses yielded strikingly similar positive associations between IGF-1 and breast cancer as those found in our observational analyses. Taken together, these results provide the strongest evidence to date for a causal role of the IGF-pathway in breast cancer development and suggest that altering IGF-1 levels through diet and lifestyle or pharmacological means may be an effective strategy in the primary prevention of breast cancer. Our next step is to gain a fuller understanding of which lifestyle practices can alter IGF-1 concentrations and, in turn, the chances of breast cancer developing."

It may be possible to modify IGF-1 concentrations in the blood through changes to the amount and types of proteins in a person’s diet, according to the press release. In addition, drugs that target the IGF-1 system have been developed.

Reference

• Higher concentrations of IGF-1 are a probable cause of breast cancer [news release]. Medical Express website. Published March 11, 2020. https://medicalxpress.com/news/2020-03-higher-igf-probable-breast-cancer.html. Accessed March 13, 2020.