Can genes explain the link between obesity and progression of prostate cancer?

Obesity is becoming a common issue in most industrialized nations, with the prevalence in the United States, for instance, reaching over a third of the population, while deaths linked to obesity in the UK have risen dramatically, highlighting the important relationship between obesity and health. Diseases associated with obesity represent a significant medical and financial burden, and include diabetes, cardiovascular disorders and certain cancers.

There is much data that indicates a direct association between obesity and the risk of developing cancer, and for certain cancers, such as pancreas and breast cancer, this link is well established. The link between obesity and prostate cancer, however, is still under debate, although there have been recent studies that have demonstrated that obesity is related to more aggressive prostate cancer as well as worse clinical outcomes. It has been suggested that is due to the influence of the periprostatic (PP) adipose tissue which surrounds the prostate on the growth and progression of the cancer cells. In an attempt to unravel the mechanisms behind this association, Dr Ricardo Ribeiro and colleagues sought to determine whether the relationship between obesity and prostate cancer aggressiveness is due to changes in the genetic characteristics of this tissue. Such evidence would provide a genetic link for the association between obesity and prostate cancer.

In a small but elegant study published in BMC Medicine, the authors compared the gene expression profiles within the PP tissue of three groups of patients; those with benign prostate tumors, those with prostate cancer that was confined to the prostate, and those whose prostate cancer had metastasized. In each group of six individuals, half were lean and half were obese or overweight. They found that, compared to the lean patients, the genes expressed in the obese patients created a favorable environment for a more aggressive cancer by reducing immune surveillance and increasing cell expansion. In the prostate cancer patients, they found that genes such as those involved in anti-apoptosis were up-regulated. This promoted an increase in the PP adipose tissue thickness, which has been previously shown to also foster tumor aggressiveness. Overall, the results indicate that there may be “cross-talk” between PP adipose tissue and prostate cancer cells that may result in faster disease progression, which is especially apparent in obese patients.

This important study has identified genetic pathways that can influence prostate cancer progression. As well as potentially providing novel therapeutic targets, this information can be used to stratify patients according to prognosis and treat them appropriately. These issues are discussed in an accompanying commentary to this research by Professor Giovanni Lughezzani. Furthermore, this study provides insight into how obesity can contribute to cancer progression by changes in the local microenvironment, and can lead to preventative strategies to decrease the burden of obesity-related cancer.

Both papers are the latest additions to the article collection Metabolism, diet and disease. This series is aimed at demonstrating that basic research on the biochemistry, cell biology and genetics of metabolism can be translated to address the major health problems of obesity and diet related disorders such as cancer. The therapeutic and nutritional implications associated with these findings can inform the clinical management and treatment of these diseases.

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