By Ashley Brenton, PhD
The foundation of Precision Medicine is to use an individual’s unique genetics to predict their
risk for developing disease. In particular, individual genetic variants are increasingly implicated
in the risk for various cancers. The most famous of these, and first discovered, were the BRCA1
and BRCA2 variants for breast cancer. A present, there are hundreds of such risk variants
known for a variant of cancers. This growing knowledge contributes to the realization of
A new paper, “Meta-analysis of five genome-wide association studies identifies multiple new
loci associated with testicular germ cell tumor,” published in Nature Genetics, reveals eight new
genetic locations, or loci, implicated in testicular germ cell tumor risk. The study, a meta-
analysis of five genome-wide association studies (GWAS), was conducted by a global group of
researchers and the International Testicular Cancer Consortium. This study contributes to the
growing body of evidence demonstrating a link between inherited genetics and cancer risk.
It has been recognized for some time that there is a familial link to testicular cancer, as disease
risk increases if a man’s father or brother has been diagnosed. This has led scientists to try to
identify those risk markers, or the loci, that increase risk of cancer. Information like this can be
used in precision medicine to identify those at risk of cancer through screening, to detect
cancer early and to provide information about treatment.
The eight loci identified—chromosomal locations 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13,
15q21.3, 15q22.31, and X128—are involved in sperm development. Functionally, it makes
sense that mutations in sperm producing areas may be involved in the development of
testicular cancer. One shortcoming of many GWAS studies is that the relevant function of the
identified mutations or loci is not immediately apparent. The loci may occur in completely
separate body systems. Of course, this speaks to the complexity of systems biology and will
become more useful as the human genome is further annotated. For the eight loci identified, it
remains to determine exactly what genetic variants in these regions cover the risk. This will be
essential before they can be widely used identity individuals at greater risk.
Testicular cancer is rare, affecting fewer than 9,000 Americans annually. However, the majority
of testicular cancer cases occur in men younger than 40 years old. According to the American
Cancer Society, 90% of testicular cancer develops in germ cells, and there are two main forms
of testicular germ cell tumors: seminomas and non-seminomas. The two types of germ cells
tumors spread differently and are sometimes treated differently. A microscopic examination of
the tumor can determine which type of germ cell tumor is present. In the US, about 50% of
testicular germ cell tumors are seminomas and 50% are non-seminomas.
Wang Z, McGlynn K, Meyts E, Bishop D, Chug C, Dalgaard, et al. “Meta-analysis of five genome-
wide association studies identifies multiple new loci associated with testicular germ cell tumor.”
Nature Genetics 49, 1141-1147 (2017).
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Dr. Ashley Brenton is a precision medicine veteran. A classically trained molecular biologist, Dr.
Brenton’s career has focused on applying genomics to public health issues and she has a proven
track record in building scientific evidence for precision medicine, as well as bringing successful
precision medicine tests to commercialization. Dr. Brenton began her career at Johns Hopkins
and her background in public health and genomics led her to Soteria, where she strives to help
patients and their families navigate the often-complicated world of medicine through clear
communication and an expert understanding of cutting-edge medical testing.