New Study Links Testicular Cancer Risk to Rare Genetic Variants Involved in Cell Structure and Movement

New Study Links Testicular Cancer Risk to Rare Genetic Variants Involved in Cell Structure and Movement

(IN BRIEF) The largest study to date on testicular germ cell tumours (TGCTs) has revealed a potential link between testicular cancer risk and rare genetic variants affecting cellular movement and structure. Conducted by The Institute of Cancer Research, London, the study found that these low-frequency genetic disruptions, while not pointing to a single high-risk gene, may collectively elevate cancer risk. These findings pave the way for improved risk prediction and highlight the need for larger datasets to further understand TGCT heritability and biology.

(PRESS RELEASE) LONDON, 25-Apr-2025 — /EuropaWire/ — A landmark genetic study led by researchers at The Institute of Cancer Research (ICR), London, has uncovered a possible link between testicular cancer susceptibility and rare inherited gene variants involved in cell shape and movement. Focusing on testicular germ cell tumours (TGCTs), which account for over 90% of all testicular cancer cases, the study is the largest of its kind and sheds new light on the complex genetic underpinnings of the disease.

Published in European Urology Open Science, the research analysed whole-exome sequencing data from 1,435 TGCT patients and 18,284 cancer-free controls. The team found an enrichment of rare, protein-disrupting variants in genes related to microtubular and ciliary function—structures crucial to how cells move and function. While no single gene reached statistical significance, the analysis revealed broader genetic pathways that may influence disease risk, setting the stage for future therapeutic targets and improved risk assessment strategies.

Testicular cancer, although highly treatable with survival rates above 95%, has one of the highest heritability rates among cancers—between 37% and 49%. This study reaffirms that genetic factors play a substantial role in susceptibility, especially among men with close family members affected by the disease.

First author Zeid Kuzbari, PhD student at ICR, stated: “Although this study didn’t pinpoint a specific gene, it’s a meaningful step forward in understanding the genetic architecture of TGCT. Our findings indicate that risk likely stems from a constellation of low-impact genetic variants rather than a single high-risk mutation.”

The study benefited from enhanced datasets, including contributions from the UK Biobank, The Cancer Genome Atlas, and earlier ICR-led projects, supported primarily by the Movember Foundation and ICR’s own funding. Despite the robust scale of the study, researchers highlight the difficulty of confirming associations for rare genetic variants—a challenge often attributed to the “Winner’s curse” in early genetic discovery.

Professor Clare Turnbull, senior author and Professor of Translational Cancer Genetics at ICR, emphasized the importance of larger cohorts: “We are now analysing samples from 8,000 TGCT patients in a follow-up study. These expanded datasets, alongside more sophisticated analytical models, will help us unravel the genetic factors driving this disease and improve patient outcomes through more precise risk prediction and early detection.”

Media Contact:

Tel: 0203 437 3502
email: mediaoffice@icr.ac.uk

SOURCE: The Institute of Cancer Research