Réseau Structurant Sur le Cancer de la Prostate du Grand Ouest

Relevance and strategic approach Prostate Cancer (PCa) is the most common cancer in men and the second leading cause of cancer deaths in western countries. Known risk factors are advanced age, ethnic origins and positive family history of the disease (1). There are considerable ethnic disparities in PCa risk, with a 60% higher incidence rate among African-American (AA) men as compared with European-American (EA) men (2). Similarly, in the French West Indies, where at least 90% of inhabitants are of African descent, the incidence of PCa is twice as high as in the rest of France (3). Many lifestyles, environmental and occupational related risk factors including obesity, diet, medications and pesticides have been implicated in PCa etiology, but their roles remain unclear (4). Current research suggests that there is a complex interplay of genetic and environmental factors that have a causative role in PCa.

PCa also has a highly heterogeneous potential of evolution. While some cancers will behave in an aggressive manner, other patients will have an indolent form of the disease that could not require any treatment. Several parameters are used to predict the risk of evolution in PCa patients, either before any treatment: clinical stage, Gleason score on biopsies, and serum prostatic specific antigen (PSA), or after the analysis of radical prostatectomy specimens: pathological stage and surgical Gleason score (5). However, despite the value of these prognostic factors, the potential of aggressiveness remains difficult to assess at diagnosis, and patients classified within the intermediate risk group are often difficult to manageThere is a challenge to discover new markers and novel targets for early therapeutic manipulation.

Both genetic and environmental factors have been linked to the risk of aggressive disease. The ethnic origin is likely to play a role, since the proportion of cases diagnosed at the metastatic stage is reported to be higher for African-American patients (35%) than for European-American patients (22%), with a 2.4-fold higher mortality rate in AA men than in EA men (2).Together with genetic factors, environmental factors also seem to play a key role in PCa progression. Some environmental factors such as obesity have been associated with aggressive PCa (6). However, much remains to search about the role of genetic and environmental factors and their interplay in PCa aggressiveness. White adipose tissue (WAT) and lipids are potentially involved in the development and/or progression of PCa at many levels.

WAT is a metabolically active endocrine organ. Adipocytes secrete a variety of hormones, bioactive peptides and cytokines, termed adipokines (9). Several adipokines have been involved in the mechanisms leading to PCa progression and aggressiveness, including leptin, interleukin IL-6 and vascular endothelial growth factor (VEGF).

Storage of endocrine disruptors. Endocrine disruptors (ED) are thought to be involved in prostate cancer (10). However, epidemiologic evidence of a positive link between environmental exposures to ED is limited. Two studies using blood plasma or abdominal fat for monitoring persistent pollutants have shown positive associations with PCa risk (transchlordane, beta-hexachlorocyclohexane, trans-nonachlore, dieldrine, and polychlorinated biphenyl 153) (11, 12). A recent study carried out in French West Indies showed that chlordecone, an organochlorine pesticide with well defined estrogenic properties, increases the risk of PCa, and is associated with an aggressive form of the disease in subjects with a positive family history of PCa (13).