A meta-analysis spearheaded by The International Testicular Cancer Consortium has identified new susceptibility loci in the human genome that can increase a person’s risk of developing inherited testicular germ cell tumors.
A meta-analysis spearheaded by The International Testicular Cancer Consortium has identified new susceptibility loci in the human genome that can increase a person’s risk of developing inherited testicular germ cell tumors (TGCT).
According to the American Cancer Society, the incidence of testicular cancers has been growing in the United States, with an estimated 8850 new diagnoses and 410 deaths from the disease in 2017. Although not a common disease (incidence is 1 in every 263 males), TGCT is more common among young and middle-aged men, with the average age at diagnosis being 33 years.
The global incidence of the disease has seen a rise as well, with the number of diagnosis growing by 54% between 1973 and 2003. Additionally, the geographic prevalence of TGCT has identified a higher incidence among men with a Northern European ancestry, while the disease is less common among men of African descent. Studies have also found that men who have a father with TGCT have a 4-times greater risk of developing the disease, a risk which increases to 8-fold if they have a brother with TGCT.
For their current analysis, the study team evaluated a total of 3558 cases of TGCT along with 13,970 controls. The fixed-effects meta-analysis, which included an evaluation of genetic abnormalities on the X chromosome, identified 8 new loci that achieved a genome-wide significance: 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28. The authors write that most of these loci “harbor biologically plausible candidate genes,” meaning they are potentially druggable. They also identified 4 independent single-nucleotide polymorphisms in previously identified regions.
Katherine L. Nathanson, MD, professor of Translational Medicine and Human Genetics at the Perelman School of Medicine at the University of Pennsylvania and a member of Penn's Abramson Cancer Center, pointed out that the identified loci have known biological significance and disrupt pathways that are involved in the development, maturation, and function of male germ cells. The authors report that the 40 identified loci for TGCT can now account for 37% of the father-to-son familial risk of testicular cancer, 8% of which are the 12 new signals that were identified by the current meta-analysis.
“These findings can guide us when trying to determine which patients are at a high risk of developing disease and who among them should be screened,” Nathanson said.
The study results have been published in Nature Genetics.