Prostate cancer is the most common cancer in men in Europe. Recent studies have observed that risk factors for prostate cancer may be different for low risk (indolent) than for aggressive (clinically significant) tumors. Although a lot of effort has been put into identifying factors which may affect the chance of developing prostate cancer, to date we don’t know what to tell men who want to reduce their prostate cancer risk.

Greater height and obesity have been suggested as possible prostate cancer risk factors, but these associations are not clear, probably because most previous studies have not looked separately at different tumor subtypes. To tackle this issue, we need more studies splitting tumors into subtypes accordingly to both how far the tumor has spread (tumor stage) and how abnormal the cells are compared to normal cells (histological grade).

Our study shows that taller men (height > 181.0 cm) have a 54% higher risk of being diagnosed with high-grade prostate cancer

In our study we investigated the associations of height and obesity with prostate cancer by different tumor characteristics and with prostate cancer death in 141,896 men from 8 European countries from the EPIC cohort. After 14 years of follow-up, there were 7024 participants with prostate cancer and 934 prostate cancer deaths.

We found a marked difference in risks looking at low and high risk tumors. Taller men and men with greater obesity had an elevated risk of high-grade prostate cancer and prostate cancer death. What is particularly important is the stronger findings for high grade than for advanced stage (which had been previously grouped together), emphasizing the need to look separately at tumors according to stage and grade.

Our study shows that taller men (height > 181.0 cm) have a 54% higher risk of being diagnosed with high-grade prostate cancer and a 43% higher risk of dying from prostate cancer than shorter men (height < 168.5 cm). This finding may provide insights into the mechanisms underlying prostate cancer development, for example related to early nutrition and growth.

We also found that greater adiposity (BMI > 29.2 kg/m²) was associated with a 32% higher risk of high grade prostate cancer and a 35% higher risk of prostate cancer death, and the association of waist circumference with risk was even stronger (43% higher risk for high grade prostate cancer and 55% higher risk for prostate cancer death). Several mechanisms, such as sex hormones and growth factors, may be behind this association.

The importance of looking separately at different subtypes of aggressive cancers

It is not only important to look separately at non-aggressive and aggressive tumors, but also to split tumors into subtypes accordingly to both tumor stage and histological grade. However, in the majority of studies stage and grade have been grouped together in combined categories of aggressive (advanced stage and/or high grade) or non-aggressive (non-advanced stage/low grade) tumors.

Understanding prostate cancer stage is easy; if the cancer has spread outside the prostate we called it advanced stage, and if it is contained within the prostate capsule we called it localized stage.

However, prostate cancer grade might be more difficult to understand. To determine prostate cancer grade the pathologist looks at several biopsies from the prostate of a patient and then grades each sample of prostate cells from 1 to 5 according how much the cancer cells look like normal cells, as shown in the figure below. Then the pathologist works out an overall score (called Gleason sum) by summing the 2 most common grades. For example, if the most common grade is grade 3, and the second most common is grade 2, then the overall Gleason sum is 5.

In our study we used a strict definition to be sure that we have identified correctly high-grade tumors. As indicated in the figure, we defined grade as low-intermediate if the Gleason sum was < 8 or grade was coded as well, moderately or poorly differentiated by the pathologist. And we defined high-grade tumors as those with a Gleason sum ≥ 8 or if grade was coded as undifferentiated.

Take home message

Our results emphasize the importance of studying risk factors for advanced stage and high grade tumors separately when assessing risk factors for prostate cancer. There is nothing men can do about their height, but at least it is now more evident that they may reduce their prostate cancer risk by having a healthy weight. However, further research is still needed to understand possible mechanisms, such as hormonal alterations, and to establish whether the associations we have seen are causal.”