Fat tissue and advanced prostate cancer risk

Grant title: Periprostatic adipose tissue and advanced prostate cancer risk; a prospective study

Background

Obesity is associated with increased risk of aggressive prostate cancer, but the exact mechanisms contributing to this relationship are not completely understood.

Excess fat surrounding internal organs is now understood to be harmful to health, and the prostate is no exception in being enveloped by a layer of fat. This so-called periprostatic fat is difficult to measure due to its location within the pelvis and can only be assessed using imaging techniques.

As such, how the amount of periprostatic fat varies between individuals has never before been assessed in a healthy population, and its relationship with prostate cancer risk is unknown.

We hypothesize that an increased amount of fat around the prostate is associated with increased risk of aggressive prostate cancer.

Aims and Objectives

The aim of this project is to examine the amount of fat surrounding the prostate as a risk factor for aggressive prostate cancer. Our objectives:

1. To measure periprostatic fat in healthy men and to describe the characteristics of men with increased amounts of this fat type
2. To identify genetic predictors of increased periprostatic fat, and use a so-called Mendelian Randomization analysis to determine their relationship with aggressive prostate cancer
3. To examine whether men with higher amounts of periprostatic fat are at increased risk of aggressive prostate cancer

How it will be done

This project will analyse whole body imaging scans uniquely available in large groups of healthy men participating in UK Biobank and Icelandic AGES-Reykjavik studies to measure the quantity and assess the characteristics of periprostatic fat.

The individuals in both studies have now been followed for over a decade, over which time hundreds of aggressive cases of prostate cancer have been newly diagnosed. We will identify small alterations in the genetic code of these individuals that predict an increased amount of periprostatic fat.

Using data from a consortium or large group of multiple studies examining the relationship between genetics and prostate cancer we will perform a so-called Mendelian randomisation analysis to test whether the genetic code for increased periprostatic fat is associated with increased risk of aggressive prostate cancer.

We will apply rigorous statistical methods to examine whether men with increased amounts of fat around the prostate are at higher risk of being diagnosed with a more aggressive form of prostate cancer.

These complementary approaches will result in a robust understanding of the relationship between periprostatic fat and aggressive prostate cancer risk.

Potential impact

Our study will test, for the first time, whether an increased amount of fat surrounding the prostate could affect a man’s future risk of being diagnosed with a more aggressive prostate cancer.

Identifying lifestyle characteristics of men with higher amounts of periprostatic fat could suggest possible lifestyle modifications to reduce the size of this fat depot to potentially lower their risk of developing an aggressive prostate tumour.

More insight into the relationship between periprostatic fat and aggressive prostate cancer could lead to intervention studies and, ultimately, will inform future policies to prevent aggressive prostate cancer.

Excess fat surrounding internal organs is now understood to be harmful to health. The prostate is no exception in being enveloped by a layer of fat, but the relationship of this so-called periprostatic fat to aggressive prostate cancer risk has never been tested.
Dr Emma Allott