Genes & Testicular Cancer Risk

Genes & Testicular Cancer Risk

Ongoing research identifying genes associated with an increased risk of testicular cancer has new findings. Here’s what they are and what young men should know about this form of cancer. 

Cancer risk rises with age. Overall, older people are more likely to be diagnosed with the disease. For young men, there’s one exception. It’s testicular cancer, and, while generally rare and highly treatable, its incidence is rising. Self-examination can discover the cancer early. Unfortunately, this can also lead to over diagnosis. While treatment is usually successful at the later stages, the disease sometimes requires surgery or even chemotherapy. That’s why finding a clear risk factor is so important. Ongoing research identifying genes associated with an increased risk of testicular cancer has new findings. Here’s what they are and what young men should know about this form of cancer. 


The Risk to Young Men


All cancers begin when genetically damaged cells continue to divide and multiply rather than dying off. While some cancers are slow growing, others spread quickly. Age is a driving factor for most cancers. Although cancer affects seniors at a rate of 1,000 people out of 100,000, it’s less than 100 per 100,000 for those in their 20s. For young men between the ages of 15 and 35, testicular cancer is the most common form of the disease. It occurs within the testes, which are part of the male reproductive system along with the prostate gland, seminal vesicles, and penis. The testicles are responsible for the production of hormones and sperm. Even when testicular cancer has metastasized or spread beyond its original location, it is highly treatable. 


Although there are steps people can take to reduce their risk of getting certain cancers like those of the lung, kidney, or prostate, there are no known behavioral or lifestyle changes that can reduce a young man’s risk of developing testicular cancer. Other than having an undescended testicle or abnormal testicular development, the primary risk factor is being young and White (it affects Black men less often.) The main driver is family history and genetics. That’s why research by the international TEsticular CAncer Consortium (TECAC) is so important. 


Some 95 percent of testicular cancer cases are due to germ cell tumors––or a kind of tumor that begins in a man’s sperm. These tumors are the most common form of cancer for White men between the ages of 20 to 39 and a rising form of cancer for Latino men as well. That’s why determining a man’s risk at the genetic level can be so beneficial. As researchers’ abilities to identify genetic markers for certain diseases improve, they have been able to link certain genes to an elevated cancer risk. Women who have inherited mutations in the BRCA1 and BRCA2 genes have a higher risk for breast and ovarian cancer, while those with mutations of cell cycle regulator CHEK2 have twice the risk of breast cancer as someone without the mutation. Some women, upon learning they possess these mutations, have taken aggressive steps, including preventative mastectomies, in order to avoid getting this often fatal disease. 


For men, the risk is different. Although some doctors still advise men to self exam and report any unusual masses or lumps, other health care professionals disagree. That’s because often those suspicious masses are benign. Screenings and self exams can lead to overdiagnosis––which is when a patient undergoes expensive, painful, and/or invasive treatment for something that may not cause them any physical harm. On the other hand, while testicular cancer is rarely fatal even if it spreads beyond the testes, treatment can include surgery or chemotherapy which has numerous uncomfortable side effects. 


Finding The Genes


Identifying who is most at risk and thus better served by additional medical scrutiny has been an ongoing project for the international TEsticular CAncer Consortium (TECAC). In 2017, TECAC researchers had identified a dozen genetic markers for inherited testicular cancer. Recently, they conducted a meta-analysis that increased the number of genetic locations for the disease by TECAC identifying 40 percent


Genome-wide association studies (GWAS), like the one done by TECAC, identify common variations that can be linked to an increased risk for certain diseases. The team discovered locations on chromosomes holding variants that could be connected to increased germ cell tumor risk. After analyzing the genetic data from over 10,000 testicular germ cell tumor cases against almost 200,000 healthy controls, TECAC was able to find a total of 78 of these loci. As the research’s leader, Katherine L. Nathanson, MD. deputy director of Penn’s Abramson Cancer Center and Pearl Basser Professor of BRCA-Related Research in the Perelman School of Medicine at the University of Pennsylvania, points out, “This latest set of genetic locations is adding to our understanding of the inherited drivers of testicular cancer,” which can identify men at greater risk for the disease––meaning early detection rather than later surgery or chemo. 


As the study explained, by establishing multiple genes that put men at a higher risk of disease, screening can be focused on those most likely to get the disease. Those with the most genetic markers are almost seven times as likely to get testicular cancer. When that’s applied to men with other risk factors, the number who need medical scrutiny drops considerably. That means fewer tests for most men and earlier, less invasive treatment for those who need it the most.