Higher Levels of IGF-1 and Free Testosterone Increase the Risk of Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with Prostate cancer during their lifetime. It is estimated that in the United States, about 174,650 new cases of Prostate cancer will be diagnosed in 2019 and 31,620 men will die of the disease. The etiology of Prostate cancer remains unclear, and North American Blacks are at the highest risk whereas risk is lowest in Asians, with the risk among Caucasians somewhere in between.

The Insulin-like Growth Factor (IGF) system has been reported to regulate normal and malignant cell growth, proliferation and differentiation, tissue homeostasis and cellular metabolism, and its relevance in carcinogenesis has been well established. The role of IGF system in Prostate cancer was initially recognized from epidemiological studies which showed that higher serum IGF-1 concentrations correlated with an increased risk of Prostate cancer. Testosterone in the circulation is bound primarily to Sex Hormone Binding Globulin (SHBG) while the unbound, or free testosterone, is the most bioavailable and active form.

The authors in this large prospective study investigated the association of circulating levels of IGF-I, free (biologically active testosterone) and total testosterone, and Sex Hormone Binding Globulin (SHBG) with Prostate cancer incidence and mortality, in a large cohort of patients. This study included 200,452 male participants who were free of cancer when they were enrolled in the study, and were not taking any hormone therapy. Baseline blood samples were obtained from these men and tested for levels of total testosterone and IGF-1. Free testosterone level was calculated from measured total testosterone and binding protein concentrations.

After a mean follow up of 6.9 years, 5412 men were diagnosed with Prostate cancer and 296 had died from the disease. It was noted that higher levels of circulating IGF-I was associated with an elevated risk of Prostate cancer diagnosis, as well as Prostate cancer mortality. Higher free testosterone level was associated with an elevated risk of incident Prostate cancer, whereas higher SHBG was associated with a lower risk, but neither was associated with Prostate cancer mortality. Total testosterone levels were not associated with Prostate cancer incidence or mortality. For every 5 nanomoles increase in the concentration of IGF-1 per liter of blood (5 nmol/L), men were 9% more likely to develop Prostate cancer. For every 50 picomoles increase of free testosterone per liter of blood (50 pmol/L), there was a 10% increase in Prostate cancer risk. The researchers added that their findings correspond to a 25% greater risk of Prostate cancer in men who have the highest levels of IGF-1, compared to those with the lowest, and men with the highest free testosterone levels have a 18% greater risk of Prostate cancer, compared to those with the lowest levels.

It was concluded from this study that circulating levels of IGF-I and free testosterone play a role in the development of Prostate cancer and these two hormones could be one of the several mechanisms that links diet, lifestyle, and body size with the risk of Prostate cancer, taking us one step closer to Prostate cancer prevention. Serum hormones and prostate cancer incidence and mortality in UK Biobank. Travis R, Watts E, Fensom G, et al. Presented at the 2019 NCRI Cancer Conference. Abstract#2904