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For many years, global health has been associated with diseases like HIV/AIDS and malaria. And rightly so. These diseases present significant threats to health around the world. But they aren't the only major killers. In fact, they're not even the leading killers anymore! Today, cancer claims more lives globally than HIV/AIDS, malaria, and tuberculosis combined, and the death toll from cancer is only going to grow.
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Testicular Cancer News |
Penn Medicine researchers identify 4 new genetic risk factors for testicular cancer
May 13, 2013 Viewed: 395
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.
Abnormal testicle development. Conditions that cause testicles to develop abnormally, such as Klinefelter's syndrome, may increase your risk of testicular cancer.
Family history. If family members have had testicular cancer, you may have an increased risk.
Age. Testicular cancer affects teens and younger men, particularly those between ages 15 and 34. However, it can occur at any age.
Race. Testicular cancer is more common in white men than in black men.
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."
Undescended testicle
The most important risk factor for testicular cancer is undescended testicle (cryptorchidism). In the womb, the testicles develop in a male baby's abdomen. They usually move down into the scrotum at birth, or within the first year of life. If they move down later, or need surgery to bring them down this is called undescended testicle. A review of published studies in 2012 showed that in this situation there is a 3 times increase in the risk of testicular cancer. As testicular cancer is rare, the risk is still small.
In most men the testicles move down by the age of puberty, or they have surgery to bring them down. In men where the condition is not corrected by the age of 13, the risk of testicular cancer is increased by up to 5 times.
Carcinoma in situ of the testicle
Carcinoma in situ (CIS) means that there are abnormal cells in the testicle. But they are completely contained and so cannot spread, as cancer cells can. Carcinoma in situ of the testicle is not cancer. But if left untreated, it will develop into cancer in about half the men who have it (50%). There is no lump and usually no other symptom. CIS is most often found when a man has a testicular biopsy to investigate infertility. CIS can be treated by removing the testicle, to prevent a testicular cancer from developing.
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
Provided by ArmMed Media
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