Approximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence that spermatogenesis impairment is associated with increased risk of prostate, testicular, and other cancers. Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. This narrative review covers the most recent research on prognostic markers of cancer in infertile men. These include molecular biomarkers such as genetic, epigenetic, and proteomic signatures; endocrine and hormonal profiles; and clinical predictors such as azoospermia, severe oligozoospermia, and a history of cryptorchidism. The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies.
Current issues in molecular biology. 2025 Nov 08*** epublish ***
Athanasios Zachariou, Efthalia Moustakli, Athanasios Zikopoulos, Maria Filiponi, Anastasios Potiris, Nikolaos Kathopoulis, Themos Grigoriadis, Maria Tzeli, Nikolaos Machairiotis, Ekaterini Domali, Nikolaos Thomakos, Sofoklis Stavros
Department of Urology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece., Department of Nursing, School of Health Sciences, University of Ioannina, 4th Kilometer National Highway Str. Ioannina-Athens, 45500 Ioannina, Greece., Torbay and South Devon NHS Foundation Trust, Lowes Brg, Torquay TQ2 7AA, UK., Urology Outpatient Department, KENTAVROS Rehabilitation Centre, 38222 Volos, Greece., Third Department of Obstetrics and Gynecology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece., First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece., Department of Midwifery, Faculty of Health and Caring Sciences, University of West Attica, 12243 Athens, Greece.