A Journey Through Our Genes: The Story of Prostate Cancer's Hidden Secrets

Picture the body as a grand city, with DNA as the underlying code that directs its bustling activity. Yet within this complex system, errors can emerge—tiny genetic misprints that can spell the difference between health and illness. For many men, these misprints lead to a journey with prostate cancer, a journey that can either be a silent passage or an unexpected plunge into a battle with an aggressive disease. At this juncture, it is crucial to lend an ear to Dr. Burcu Darst, an Assistant Professor in the Public Health Sciences Division at Fred Hutchinson Cancer Center. Dr. Darst and colleagues, like master codebreakers, have long sought to understand the enigmatic question that haunts both the corridors of hospitals and the quiet thoughts of those at risk: Do pathogenic variants in genes beyond the well-known suspects contribute to the risk of aggressive prostate cancer?

In recently published JAMA Oncology study that performed a large genetic association analysis of 17,546 men —navigating the maze of both aggressive and nonaggressive forms of prostate cancer—a striking finding emerged. Known genes such as BRCA2, ATM, and NBN, the usual suspects in the lineup of prostate cancer risk, were indeed implicated in the aggressive cases. But the plot thickened as nominal association evidence pointed fingers at other genes—MSH2, XRCC2, and MRE11A—hinting that they too might play a role in this complex tale. These findings illuminate a critical pathway: the genes responsible for DNA repair, those meticulous editors of our genetic manuscript, when compromised, seem to increase the likelihood of a man's story taking a turn towards a more threatening form of prostate cancer. This revelation has profound implications for how we manage prostate cancer. It is not just about catching the disease; it is about understanding its potential to evolve into something more formidable. The study suggests that men with non-aggressive prostate cancer who harbor these deleterious variants are on a precarious ledge, with a higher likelihood of their condition advancing to a stage that demands a more aggressive strategy.

What does this mean for the everyday hero facing down prostate cancer? It means that one day, a simple genetic test could provide men with a clearer picture of their prostate cancer risk, leading to better outcomes and more lives saved. It is about shifting from a one-size-fits-all battle plan to a tailored strategy, arming each individual with the knowledge of their unique genetic makeup. Yet, for all the answers this study provides, it also opens a door to new questions. How do these additional genes interact with the known risk factors? What are the best steps to take once these genetic markers are identified? The researchers' work adds vital pieces to the puzzle, but the full picture of how we conquer prostate cancer remains a work in progress. In the meantime, these insights stand as beacons of hope. They underscore the power of relentless research and the need to continue pouring resources into the quest to decode our genetic blueprints. Each discovery brings us closer to a world where the threat of cancer's aggression is met with personalized defenses, where the fear of the unknown gives way to the power of knowledge.

This research was made possible through funding by the National Cancer Institute, and Andy Hill Cancer Research Endowment Distinguished Researchers Program and a Fred Hutch/University of Washington prostate SPORE grant.

Fred Hutch/UW/Seattle Children’s Cancer Consortium member Dr. Burcu Darst contributed to this study.

Darst, B. F., Saunders, E., Dadaev, T., Sheng, X., Wan, P., Pooler, L., Xia, L. Y., Chanock, S., Berndt, S. I., Wang, Y., Patel, A. V., Albanes, D., Weinstein, S. J., Gnanapragasam, V., Huff, C., Couch, F. J., Wolk, A., Giles, G. G., Nguyen-Dumont, T., Mi. (2023). Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer. JAMA oncology, 10.1001/jamaoncol.2023.3482.