Penn Medicine researchers identify 4 new genetic risk factors for testicular cancer

A new study looking at the genomes of more than 13,000 men identified four new genetic variants associated with an increased risk of testicular cancer, the most commonly diagnosed type in young men today. The findings from this first-of-its-kind meta-analysis were reported online May 12 in Nature Genetics by researchers at the Perelman School of Medicine at the University of Pennsylvania.

The discovery of these genetic variations - chromosomal "typos," so to speak - could ultimately help researchers better understand which men are at high risk and allow for early detection or prevention of the disease.

"As we continue to cast a wider net, we identify additional genetic risk factors, which point to new mechanisms for disease," said Katherine L. Nathanson, MD, associate professor in the division of Translational Medicine and Human Genetics within the department of Medicine. "Certain chromosomal regions, what we call loci, are tied into testicular cancer susceptibility, and represent a promising path to stratifying patients into risk groups - for a disease we know is highly heritable."

Tapping into three genome-wide association studies (GWAS), the researchers, including Peter A. Kanetsky, PhD, MPH, an associate professor in the department of Biostatistics and Epidemiology, analyzed 931 affected individuals and 1,975 controls and confirmed the results in an additional 3,211 men with cancer and 7,591 controls. The meta-analysis revealed that testicular germ cell tumor (TGCT) risk was significantly associated with markers at four loci - 4q22, 7q22, 16q22.3, and 17q22, none of which have been identified in other cancers. Additionally, these loci pose a higher risk than the vast majority of other loci identified for some common cancers, such as breast and prostate.

This brings the number of genomic regions associated with testicular cancer up to 17 - including eight new ones reported in another study in this issue of Nature Genetics.

Testicular cancer is relatively rare; however, incidence rates have doubled in the past 40 years. It is also highly heritable. If a man has a father or son with testicular cancer, he has a four-to six-fold higher risk of developing it compared to a man with no family history. That increases to an eight-to 10-fold higher risk if the man has a brother with testicular cancer.

Factors that may increase your risk of testicular cancer include:

An undescended testicle (cryptorchidism). The testes form in the abdominal area during fetal development and usually descend into the scrotum before birth. Men who have a testicle that never descended are at greater risk of testicular cancer in either testicle than are men whose testicles descended normally. The risk remains even if the testicle has been surgically relocated to the scrotum. Still, the majority of men who develop testicular cancer don't have a history of undescended testicles.. Conditions that cause testicles to develop abnormally, such as Klinefelter's syndrome, may increase your risk of testicular cancer.. If family members have had testicular cancer, you may have an increased risk.. Testicular cancer affects teens and younger men, particularly those between ages 15 and 34. However, it can occur at any age.. Testicular cancer is more common in white men than in black men.