# Bridging Andrology and Oncology: Prognostic Indicators of Cancer Among Infertile Men

**Authors:** Athanasios Zachariou, Efthalia Moustakli, Athanasios Zikopoulos, Maria Filiponi, Anastasios Potiris, Nikolaos Kathopoulis, Themos Grigoriadis, Maria Tzeli, Nikolaos Machairiotis, Ekaterini Domali, Nikolaos Thomakos, Sofoklis Stavros

PMC · DOI: 10.3390/cimb47110930 · 2025-11-08

## TL;DR

Infertile men may have a higher cancer risk due to shared biological pathways, and this review explores potential markers for early cancer detection.

## Contribution

This paper reviews recent advances in identifying cancer prognostic indicators among infertile men for precision medicine.

## Key findings

- Genetic and epigenetic factors like Y-chromosome deletions and BRCA1/2 mutations are linked to cancer risk in infertile men.
- Clinical indicators such as azoospermia and cryptorchidism correlate with increased cancer susceptibility.
- Integrating these markers into risk models could improve early cancer surveillance in this population.

## Abstract

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.

## Linked entities

- **Genes:** BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672], BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675], TP53 (tumor protein p53) [NCBI Gene 7157], MLH1 (mutL homolog 1) [NCBI Gene 4292], MSH2 (mutS homolog 2) [NCBI Gene 4436]
- **Diseases:** prostate cancer (MONDO:0005159), testicular cancer (MONDO:0003510)

## Full-text entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}
- **Diseases:** reproductive failure (MESH:D051437), cryptorchidism (MESH:D003456), Cancer (MESH:D009369), azoospermia (MESH:D053713), oligozoospermia (MESH:D009845), prostate, testicular, and other cancers (MESH:D011471), Male infertility (MESH:D007248), spermatogenesis impairment (MESH:C536875)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12651320/full.md

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Source: https://tomesphere.com/paper/PMC12651320