The University of South Florida along with Moffitt Cancer Center has published a study in the October issue of Brain, Behavior, and Immunity which found that men with advanced prostate cancer who are on androgen deprivation therapy (ADT) are more likely to suffer from general fatigue if they also have single nucleotide polymorphisms in three pro-inflammatory genes.

I don’t believe that men with this genetic structure should elect to skip ADT, so the study’s importance is of limited value, but this discovery highlights the importance of personalized medicine in the treatment of advanced prostate cancer. Increasingly, we will see a man’s genetic profile being considered while deciding on treatment protocols.

“Few studies have examined the role of genes in cancer-related fatigue and none, to our knowledge, have examined genetic variation related to androgen deprivation therapy,” said study co-principal investigator Heather S.L. Jim, Ph.D., assistant member of the Health Outcomes and Behavior Program. “We found that prostate cancer patients who carry the variants of the IL6 and TNFA genes and are treated with androgen deprivation therapy are susceptible to heightened fatigue.”

Evidence from prostate cancer studies suggests that pro-inflammatory cytokines, which have been linked to fatigue in cancer patients, are influenced by testosterone. At the same time, testosterone inhibits IL6 gene expression. Androgen deprivation therapy restricts testosterone, thus we see a heightened level of fatigue. The researchers found that patients with a greater number of variants reported greater increases in fatigue and of longer duration.

“Early identification of patients with genetic risk factors can enable clinicians to provide timely interventions, behavioral or pharmacologic, to prevent or reduce fatigue,” investigator Paul B. Jacobsen, Ph.D., associate center director for Cancer Prevention & Control at Moffitt said. “This goal is consistent with personalized cancer treatment tailored to individual gene profiles to maximize benefit and minimize side effects.”

Individualization of treatment based on genetics will be of increasing value and use in the near future.

Joel T. Nowak, M.A., M.S.W.