MEDICAL: DISEASES: CANCER: TESTICULAR CANCER: Second Gene Linked to Familial Testicular Cancer

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MEDICAL: DISEASES: CANCER: TESTICULAR CANCER: Second Gene Linked to Familial Testicular Cancer

David P. Dillard
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MEDICAL: DISEASES: CANCER: TESTICULAR CANCER:
Second Gene Linked to Familial Testicular Cancer



Date: Mon, 29 Jun 2009 09:35:23 -0400
From: "NIH OLIB (NIH/OD)" <[hidden email]>
To: [hidden email]
Subject:  Second Gene Linked to Familial Testicular Cancer



U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH



NIH News Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
<http://www.nichd.nih.gov/>


National Cancer
Institute (NCI)
<http://www.nci.nih.gov/>



For Immediate Release: Monday, June 29, 2009



SECOND GENE LINKED TO FAMILIAL TESTICULAR CANCER




CONTACTS:


Robert Bock

or

Marianne Glass Miller

301-496-5133

e-mail:

[hidden email]


NCI Press Office

301-496-6641

e-mail:

[hidden email]




SECOND GENE LINKED TO FAMILIAL TESTICULAR CANCER




Specific variations or mutations in a particular can gene raise a man's
risk of familial, or inherited, testicular germ-cell cancer, the most
common form of this disease, according to new research by scientists at
the National Institutes of Health. This is only the second gene to be
identified that affects the risk of familial testicular cancer, and the
first gene in a key biochemical pathway. The study appeared online June
23, 2009, in Cancer Research.

Researchers have suspected for years that heredity plays a role in some
patients with testicular germ-cell cancer, although attempts to identify a
single gene with very strong effects have been unsuccessful thus far.
Scientists currently believe that multiple genes with weaker individual
effects--but acting together--probably influence an individual's risk of
familial testicular cancer.

Men with a family member who had a testicular germ cell cancer are at
three-to six-fold greater risk than other men of developing testicular
cancer. Although a family history of testicular cancer probably accounts
for less than five percent of all testicular cancers, the careful study of
rare familial cancer clusters has often led to important new understanding
of the non-familial versions of the same cancer.  There will be an
estimated 8,400 new cases of testicular cancer diagnosed in 2009 with
about 90 percent of them being germ-cell cancers, according to the
National Cancer Institute (NCI).

"This study contributes to our understanding of why testicular germ cell
cancer appears to run in families," said Raynard Kington, M.D., Acting NIH
Director. "The findings may also lead to new ways to identify men at high
risk, as well as more effective ways to prevent and treat testicular germ
cell cancer."

The key pathway in this disease is the cyclic AMP pathway, which regulates
how cells respond to such signals as hormones. Drugs that affect the
cyclic AMP pathway are widely available, and, in theory, could affect
progression of testicular cancer.

In this study, Anelia Horvath, Ph.D., Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), performed the
laboratory research and Larissa Korde, M.D., NCI, led the clinical cancer
genetics study which identified the multiple-case testicular cancer
families used for the DNA analysis. The NICHD and NCI are parts of NIH.

The researchers found that seven different mutations in the gene in
question, PDE11A, created abnormal versions of the PDE11A enzyme that
slowed down the enzyme's destruction of cyclic AMP.

"The mutations don't cause cancer directly, but instead appear to increase
an individual's susceptibility to developing a tumor," explained the
study's senior author, Constantine Stratakis, M.D., D.Sc., chief of
NICHD's Section on Endocrinology and Genetics. "Almost one out of every
five families we studied had a variation in the gene that affected its
functioning."

To conduct the research, Stratakis and his colleagues analyzed the portion
of the DNA from 95 familial testicular cancer patients that contains the
PDE11A gene. They found seven mutations in the cancer patients, and noted
that the rate at which they were detected was much higher than that seen
in the DNA of people without testicular cancer.

The researchers also had access to the DNA of a group of healthy men, who
had been screened for diseases of the endocrine organs, including the
testicles. None of the men who screened negative carried any of the
genetic mutations identified in the familial testicular cancer patients.
"Because this group had no mutations in PDE11A, we were more confident
that the mutations had something to do with testicular cancer," said
Korde.

Learning how disruptions in the PDE11A enzyme lead to an increased risk of
tumor formation may help researchers identify other proteins that also
play a role, Stratakis said. He indicated that a good place to look is
among other proteins in the cyclic AMP pathway.

"This research is a perfect example of how effective medical research can
be when investigators from multiple, different disciplines work together
as a team to solve a problem," said Korde. "This is team science at its
best; it represents the kind of research synergy at which NIH excels."

Stratakis noted that PDE11A is also highly expressed in the prostate
gland. He and his colleagues are now undertaking the research to find the
frequency of PDE11A mutations in patients with prostate cancer.

NCI leads the National Cancer Program and the NIH effort to dramatically
reduce the burden of cancer and improve the lives of cancer patients and
their families, through research into prevention and cancer biology, the
development of new interventions, and the training and mentoring of new
researchers. For more information about cancer, please visit the NCI Web
site at


<http://www.cancer.gov>


or call NCI's Cancer Information Service at

1-800-4-CANCER

(1-800-422-6237)




The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation.  For more information, visit the
Institute's Web site at



<http://www.nichd.nih.gov/>




The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and its
programs, visit



<http://www.nih.gov>



-------------------------------



REFERENCE:


Horvath A, Korde L, Greene MH, Libe R, Osorio P, Faucz FR,
Raffin-Sanson ML, Tsang KM, Drori-Herishanu L, Patronas Y, Remmers EF,
Nikita M, Moran J, Greene J, Nesterova M, Merino M, Bertherat J, and
Stratakis CA
Functional phosphodiesterase 11A mutations may modify the
risk of familial and bilateral testicular germ cell tumors
Cancer Research
Online June 23, 2009.



##




This NIH News Release is available online at:
<http://www.nih.gov/news/health/jun2009/nichd-29.htm>.



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