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Study Finds Nearly Half of Testicular Cancer Risk Is Inherited

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Key Points

  • Testicular cancer is a strongly inherited disease, accounting for nearly half of the risk factors contributing to development of the cancer, with environmental and behavioral factors contributing to the other half.
  • The increased risk for testicular cancer comes from a large number of minor variations in an individual’s DNA rather than as the result of one faulty gene.
  • Identifying more genetic causes could increase screening for high-risk individuals, raising the possibility of preventing the cancer or finding the disease at an early stage. 

A large European study that combined both population-based and genomic techniques to investigate the heritability of testicular germ cell tumor has found that 48.9% of all the possible factors contributing to risk for the disease are inherited. Rather than being the result of one faulty gene, according to the study findings, the increased risk comes from a large number of minor variations in an individual’s DNA. Identifying more DNA mutations could increase strategies for disease prevention. The study by Litchfield et al was published in Scientific Reports.

Study Methodology

The researchers used data from the Swedish Family-Cancer Database, which includes all individuals born after 1931 together with their biologic parents, totaling 15.7 million individuals, and including 9,324 cases of testicular cancer. They then applied Genome-Wide Complex Trait Analysis to 986 cases diagnosed with the disease and 4,946 population controls to estimate the heritability of testicular cancer.

Study Findings

The researchers’ combined analysis found that 48.9% (95% confidence interval [CI] = 47.2%–52.3%) of all the possible factors contributing to testicular cancer risk are inherited and that the inherited risk comes from a large number of minor variations in a person’s DNA rather than as a result of one faulty gene mutation. According to the authors, there is “unequivocal evidence that a significant number of additional testicular germ cell tumor risk SNPs [single nuceleotide polymorphisms] remain still to be discovered.”

“Our results demonstrate that [testicular germ cell tumor] is a strongly heritable cancer, with a polygenic model of disease susceptibility. Although environmental factors must play a key role in the development of [testicular germ cell tumor] risk, our data suggests that genetic factors contribute significantly to disease etiology. Our findings quantify the total impact of common variation on [testicular germ cell tumor] risk, suggesting a significant number of additional risk loci remain to be discovered. Full mapping of all common SNPs associated with [testicular germ cell tumor] may plausibly offer utility in enabling personalized risk profiling for the disease, through construction of polygenic risk scoring models, as implemented in other cancer types. Overall, our findings provide a strong rationale for continuing the search for additional novel risk variants through genome-wide associated studies-based strategies,” concluded the researchers.

Clare Turnbull, MD, PhD, Senior Researcher in Genetics and Epidemiology at the Institute of Cancer Research in London, is the corresponding author of this study.

The study was funded by the Movember Foundation, the Institute of Cancer Research, and Cancer Research UK. The study authors declared no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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