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.
Given this, researchers continue to investigate genetic variants and their association with cancer.
In 2009, Dr. Nathanson and colleagues uncovered variation around two genes—KITLG and SPRY4—found to be associated with an increased risk of testicular cancer. The two variants were the first striking genetic risk factors found for this disease at the time. Since then, several more variants have been discovered, but only through single GWAS studies.
"This analysis is the first to bring several groups of data together to identify loci associated with disease," said Dr. Nathanson, "and represent the power of combining multiple GWAS to better identify genetic risk factors that failed to reach genome-wide significance in single studies."
The team also explains how the variants associated with increased cancer risk are the same genes associated with chromosomal segregation. The variants are also found near genes important for germ cell development. These data strongly supports the notion that testicular cancer is a disorder of germ cell development and maturation.
"TGCT is unique in that many of the loci are very good biological candidates due to their role in male germ cell development," said Dr. 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."
This study was supported in part by Intramural Research Program of the National Cancer Institute and the National Institutes of Health grant (R01CA114478).
Steve Graff | EurekAlert!
Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology