CANCER: Testicular

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Wednesday, June 19, 2013

4 New Genetic Risk Factors Identified For Testicular Cancer

Main Category: Cancer / Oncology
Also Included In: Men's Health;??Genetics
Article Date: 14 May 2013 - 1:00 PDT Current ratings for:
4 New Genetic Risk Factors Identified For Testicular Cancer
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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 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."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. This study was supported in part by Intramural Research Program of the National Cancer Institute and the National Institutes of Health grant (R01CA114478).
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Friday, May 31, 2013

Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy

Editor's Choice
Academic Journal
Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 17 May 2013 - 0:00 PDT Current ratings for:
Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy
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A long-term study of men with stage I seminoma, a common form of testicular cancer, suggests that surveillance for cancer recurrence, rather than additional chemotherapy or radiation therapy, is sufficient for the vast majority of patients who have undergone successful surgery for their cancer.

In a new long-term study conducted in Denmark, researchers analyzed a national clinical database and found that 99.6% of patients who only underwent surveillance (following a successful surgery) were alive after 10 years of being diagnosed with testicular cancer.

Surveillance means carrying out routine CT scans, physical exams, chest X-ray exams, and blood tests for a period of five years after surgery.

In some countries, such as Denmark (where the study took place), the preferred follow-up strategy is surveillance alone. In the U.S. half of patients undergo either radiotherapy or chemotherapy as follow-up treatment, while the other half only receive surveillance.

There has been a recent increase in the number of patients undergoing surveillance alone in the U.S., a trend that will likely continue following this new finding.

Treatment options such as chemotherapy or radiotherapy can cause very harmful side effects, including a higher risk of secondary cancers (such as leukemia). Therefore, other follow-up strategies that don't incur such drastic risks, such as surveillance alone, are preferred.

Mette Sakso Mortensen, MD, a PhD student at the Department of oncology at the Copenhagen University Hospital in Copenhagen, Denmark, said:

"To our knowledge, this study is the largest to address this issue in patients with stage I seminoma, and with the longest follow-up. Now we have solid proof that surveillance is safe and appropriate for most patients with this particular cancer.
We also characterized key prognostic factors for relapse, which can help us identify high-risk patients who may need adjuvant therapy instead of surveillance. However, in general, seminoma stage I patients can safely be followed on a surveillance program."

A total of 1,822 men with stage I seminoma, who underwent successful surgery were followed on a five year surveillance program. The researchers were able to follow the patients for an average of 15.4 years.

19.5 percent of the patients experienced a relapse, of whom 216 received radiotherapy while 136 received chemotherapy and only 3 underwent surgery.

The 10-year-cancer-specific survival rate was 99.6 percent, which translates into four men dying out of every 1,000 who underwent surveillance alone.

The risk of relapse increased among patients whose tumor size was bigger than 1.5 inches and spread to lymphatic vessels or blood, as well as those whose levels of a blood marker called human chorionic gonadotropin were high.

Even though testicular cancer is quite rare among the general population, it is the most common solid tumor among young men. Approximately 4,000 people will be diagnosed with stage I seminoma this year in the U.S.

ASCO President-Elect Clifford A. Hudis, MD, said:

"This important study is one of several recent reminders that sometimes "less is more? in patient care. Opting for surveillance spares patients, most of whom are young men, from the harmful side effects of chemotherapy and radiation without diminishing their chances for a long and healthy life."

Scientists at UC Davis found that frequent CT scanning for testicular cancer surveillance was associated with secondary malignancies.

Written by Joseph Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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