Abstract
Two genome-wide association studies have approximately tripled the number of loci potentially involved in testicular cancer, one of the most heritable types of cancer.
Testicular cancer often runs in families, but researchers have pinpointed only a handful of genetic variants for this increased susceptibility. Two studies published in Nature Genetics this month approximately triple the number of loci potentially involved in the disease and implicate a new category of genes in the cancer's development.
Genome-wide association studies (GWAS) previously showed 6 susceptibility loci that include genes such as KITLG, which is involved in germ cell development, and DMRT1, which helps orchestrate testicular development and germ cell division. However, estimates suggest there could be more than 100 other genes.
To uncover some of these loci, a team led by Katherine Nathanson, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, started by analyzing 340 candidate single-nucleotide polymorphisms (SNPs) revealed by 3 prior GWAS analyses. To winnow the list, the team reported, they scrutinized additional GWAS data and genotyped nearly 2,000 additional testicular cancer patients.
Working independently, Clare Turnbull, MD, of the Institute of Cancer Research in London, UK, and colleagues reported on results from examining the 1,050 most promising SNPs from their previous GWAS and then testing for the variants in more than 1,000 men with testicular cancer.
In total, the 2 teams identified 12 additional testicular cancer risk loci. Among the genes pinpointed by the studies are RFWD3, which shields the tumor suppressor p53, and PITX1, the third telomerase-related gene linked to testicular cancer.
Nathanson's team also identified a class of genes that hasn't been connected to the disease before. “We have identified genes which encode proteins involved in chromosomal segregation,” such as MAD1L1, she says.
Genetic testing for the identified risk variants could benefit some patients. Testicular cancer is rare, so screening the general population probably wouldn't be helpful, Nathanson says. However, she adds that such tests might help identify particularly susceptible men among those with high-risk factors such as cryptorchidism (undescended testicles).
The discovery of new susceptibility loci may present another benefit, she adds. As researchers sharpen their picture of the disease's genetics, they may be able to pin down the environmental influences that have led to a doubling of the cancer's incidence in the last 30 years.
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