Two-hormone combo test predicts prostate cancer risk

By Dr. Liji Thomas, MDNov 3 2019

New research presented at the NCRI Cancer Conference, 2019, shows that free testosterone and insulin-like growth factor-1 (IGF-I), when present at high levels in combination, show a higher risk of prostate cancer in men. This finding is important since both these factors can be counteracted, to possibly reduce the risk.

It provides strong evidence that prostate cancer could be possibly prevented. Among malignancies, only lung cancer kills more men than this condition.

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Prostate cancer

Prostate cancer is the second most common male cancer globally. Along with high testosterone levels, it is also associated with older age, certain races, and having a family history of the illness. In most cases prostate cancer is very slow, and remains confined to the prostate gland itself. At this point it is not very serious, and does not harm the patient, growing extremely slowly. This type may never require any active treatment.

However, in some types of prostate cancer, the tumor becomes aggressive, begins to spread outside the gland, and can quickly cause death. Thus this type of prostate cancer needs to be detected early to allow full and effective treatment.

The study

The study was carried out in over 200,000 men. The data on the participating men came from the UK Biobank project, and was collected from a period dating before their cancer diagnosis, and when they were not on any hormones. At this time they gave blood samples, to be tested for these two hormones. Free testosterone is important because it is not bound to any other protein and therefore exerts its effects on the body. IGF-I is a growth hormone that stimulates cells to grow and multiply.

About 9,000 of the men also gave a second sample later, which was tested for the same hormones to help the researchers understand how the levels of these hormones varied over time, even in normal men.

The findings

Following the initial blood tests, the men were followed up for 6-7 years on average, when it was found that over 5,400 men had developed prostate cancer within this period. There were almost 300 deaths from this condition as well.

On correlating earlier hormone levels with the diagnosis at a later date, the researchers found a strong link between higher hormone concentrations and prostate cancer. They calculated that there was a 9% increased risk of prostate cancer with every 5 nmol/L increase in IGF-I. And with an increase of 50 pmol/L of free testosterone, the risk went up by about 10%.

When the researchers next compared those with the highest levels of IGF-I and free testosterone with those who had the lowest, the risk difference was very marked indeed. Those in the top percentile for IGF-I and free testosterone had a 25% and 18% higher risk, respectively, compared to those in the lowest.

Implications

The importance of this link is in the long follow-up period, and the fact that the hormone levels were high for years before the cancer developed. This seems to indicate a cause-and-effect relationship in the direction of higher hormones inducing cancerous transformation, rather than in the opposite direction. As researcher Ruth Travis says, “This type of study can't tell us why these factors are linked, but we know that testosterone plays a role in the normal growth and function of the prostate and that IGF-I has a role in stimulating the growth of cells in our bodies.”

To avoid study bias, they compensated for many factors that could modulate cancer risk, such as the body size, socioeconomic status, and diabetes mellitus. They feel that these hormones could possibly mediate the effects of body fat, lifestyle factors, and diet, on the prostate. If so, this could help evolve a protective strategy for prostate cancer.

More study is planned to confirm these conclusions, and to identify what factors cause the most aggressive types of prostate cancer. Meanwhile, prostate specialist Hashim Ahmed, who was not part of this research group, says, “These results are important because they show that there are at least some factors that influence prostate cancer risk that can potentially be altered. This study also shows the importance of carrying out very large studies, which are only possible thanks to the thousands of men who agreed to take part.“