After gleaning the genomes of 13,000 men, researchers were able to identify four new genetic variants, or mutations to the chromosome, that are linked to increased risk of testicular cancer.

The identification of the variations could help researchers identify men who are most at risk, and craft a method for early detection and prevention.

"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, lead author and associate professor in the Division of Translational Medicine and Human Genetics at Perelman School 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."

In three genome-wide association studies (GWAS), researchers conducted a meta-analysis that was published on May 12 online in Nature Genetics. They assessed 931 patients with the disease and 1,975 controls, repeated their experiment in another 3,211 patients and 7,591 controls to confirm their findings and found that four markers at 4q22, 7q22, 16q22.3 and 17q22 loci were significantly associated with causing testicular germ cell tumor (TGCT).

Interestingly, the variations found in these locations on the chromosome are not observed in other forms of cancers and are more threatening than other variants identified in breast and prostate cancers.

The study was also able to explain exactly how the genetic mutations cause disruptions; these variants were also linked to disrupting the development and maturation of germ cells, which are the cells that become the eggs in girls' ovaries or the sperm in boys.

"This analysis is the first to bring several groups of data together to identify loci associated with disease and represent the power of combining multiple GWAS to better identify genetic risk factors that failed to reach genome-wide significance in single studies," Nathanson said.

According to the American Cancer Society, approximately 7,920 new testicular cancer cases are diagnosed while 370 men are predicted to die from the dreaded disease. While research has advanced considerably, the increase in incidence rate of has doubled in the last 40 years and has been overwhelming in the United States and across the globe. Furthermore, for a man whose father or son has testicular cancer, he is four to six times as likely to develop the disease.

However, some of today's treatments are highly effective and reduces chances of dying to one in 5,000.

Previously, researchers had identified 13 regions on the genome, eight from this year alone, toppling the genetic risk of testicular cancer to 17 variants.

"TGCT is unique in that many of the loci are very good biological candidates due to their role in male germ cell development," said Nathanson. "Disruptions in male germ cell development lead to tumorigenesis, and presumably also to infertility. These conditions have been linked before, epidemiologically, and genes implicated in both of our prior studies, but this study reinforces that connection."

Source:
Chung CC, Kanetsky PA, Wang Z, et al. Meta-analysis identifies four new loci associated with testicular germ cell tumor. [published online ahead of print May 12, 2013]. Nature Genetics. 2013; doi:10.1038. Accessed May 13, 2013.