Scientists Identify Three New Genetic Variants That Increase Testicular Cancer Risk

Scientists Identify Three New Genetic Variants That Increase Testicular Cancer Risk
Main Category: Cancer / Oncology
Also Included In: Genetics; Men's health
Article Date: 14 Jun 2010 - 4:00 PDT


A study led by The Institute of Cancer Research (ICR) has identified three new genetic risk factors for testicular cancer. The findings, published online today in Nature Genetics, come during the Everyman Male Cancer Awareness Month , which aims to increase awareness and funding for vital research into testicular and prostate cancers.

Team members - from the ICR, the Wellcome Trust Sanger Institute, and the Cancer Research UK Genetic Epidemiology Units in Cambridge and at the University of Leeds - scanned the genomes of almost 1,000 men with testicular cancer and almost 5,000 apparently unaffected individuals. They found genetic variants in three regions were significantly more common in the men with testicular cancer, and confirmed the results in a further 670 sufferers and 3,500 controls. The study was funded by the Everyman Campaign, Cancer Research UK and the Wellcome Trust.

Men who have any of the new regions on chromosomes 5, 12 and 9 have an increased risk of testicular cancer. Within each region, the researchers pinpointed an interesting gene most likely to be involved in causing testicular cancer. The three genes are called TERT, ATF7IP and DMRT1.

TERT and ATF7IP are important in maintaining the correct length of the ends of chromosomes, which are called telomeres. Shortened telomeres are known to occur in many cancers and genetic variants in TERT have already been linked to other cancers, including lung, bladder, cervical, pancreatic, skin and prostate cancer. The third gene identified in this new study, DMRT1, is pivotal in sex determination and has been implicated in the development of testicular cancer in mice.

Study senior author Professor Nazneen Rahman, from the ICR, says: "The genes located in these regions give us clues to the mechanisms by which testicular cancer develops. In time this may allow us to develop new treatment options."

This study takes the number of genomic regions associated with testicular cancer risk to six, after the same team found the first three factors last year.

Lead study author Dr Clare Turnbull, from the ICR, says: "This study represents further, important progress towards identifying men who are at increased genetic risk of testicular cancer. Finding those men at highest risk may allow early detection or prevention of the disease."

The researchers are keen to recruit more men with testicular cancer to the research, for more information visit this link.

Notes

- Testicular cancer is the most common cancer in men aged 15 to 45 years

- The disease has a strong genetic component and men who have a brother affected by testicular cancer have an eight -to ten-fold increased risk of developing the disease than men without a family history. These inheritance risk factors are much higher than for other cancer types, which are generally only two-fold

- The present study found risk factors for testicular germ cell tumour at chromosome position 5p15 (TERT) (OR=1.54 (95%CI 1.33-1.79)P=1.14x10-23), chromosome position12p13 (ATF7IP) (OR=1.27 (95%CI 1.12-1.44), P=6.16x10-10) and chromosome position 9q24 (DMRT1) (OR=1.37 (95%CI 1.21-1.55), P=1.12x10-23). The manuscript Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer is being published online in Nature Genetics

- The previous study found risk factors at positions 5q31 (SPRY4), 6p21 (BAK1) and 12p21 (KITLG). A genome-wide association study of Testicular Germ Cell Tumour was published in Nature Genetics, 2009

Source
Institute of Cancer Research (ICR)

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Scientists Identify Three New Genetic Variants That Increase Testicular Cancer Risk