FAMILIAL TESTICULAR CANCER STUDY NOW RECRUITING
cancer is the most common malignancy among young men ages 15 to
35, with approximately 7,400 cases diagnosed annually in the U.S.
A few clear risk factors exist, including cryptorchidism (undescended
testicle), a prior history of cancer in one testicle (the opposite
testicle is at increased risk), and other rare conditions where
the testes develop abnormally. Among those men diagnosed with testicular
cancer, about 1-3 percent report a family history of the disease.
Brothers of affected individual are 8 to 10 times more likely to
develop testicular cancer, and men whose fathers had testicular
cancer are four times more likely to develop testicular cancer,
when compared with the relatives of men who have never had testicular
cancer. While some genetic clues are starting to emerge, the gene(s)
that cause testicular cancer have yet to be discovered.
researchers from 14 different countries have banded together in
an effort to find the gene(s) involved in causing familial testicular
cancer. They have formed an organization called the International
Testicular Cancer Linkage Consortium (ITCLC), and pooled the information
collected from the families they each identified, to do a systematic
search for these genes. In 2000, these investigators published evidence
that a familial testicular cancer gene might be located on the X-chromosome,
and they proposed that this might explain the higher risks in some
families, especially those families in which at least one of the
affected men had bilateral testicular cancer (EA Rapley et al: Nature
Genetics 2000; 24:197-200). This candidate gene has been named
the Testicular Germ Cell Tumor-1 (TGCT1) gene, and efforts to further
refine the chromosomal location and determine the DNA structure
of the gene are now underway. The gene itself has not yet been identified.
high-risk families is the major way of identifying genes that cause
diseases, and this strategy provides unique opportunities to examine
other risk factors as well. Under the leadership of Mark H. Greene,
M.D., the Clinical Genetics Branch (CGB) at the National Cancer
Institute in Bethesda, MD has recently begun to actively recruit
new families. Criteria for enrollment into the study include at
least one of the following: 1) two or more men in the family have
testicular cancer, 2) one family member has bilateral testicular
cancer (that is, separate cancers involving both testicles), or
3) one family member with testicular cancer is a member of a set
of genetically identical brothers, such as twins or triplets. Since
multiple-case testicular cancer families are relatively rare, Dr.
Greene and his colleagues have been contacting both physicians and
testicular cancer support/advocacy organizations, in an effort to
identify additional families.
part of its research strategy, the NCI study team has joined the
International Testicular Cancer Linkage Consortium. The Clinical
Genetics Branch is contributing genetic material (DNA) collected
from the new families it has identified to this international research
effort. The goal is to assemble a large enough group of high-risk
families to permit locating the proposed gene on the X chromosome,
and perhaps finding other genes as well. Eventually, it is hoped
that this research will lead to the development of laboratory tests
to identify individuals who are at increased genetic risk of testicular
The CGB team also hopes to make significant contributions to understanding
the full spectrum of the hereditary testicular cancer syndrome.
In addition to helping identify the gene or genes that cause familial
testicular cancer, they hope to better describe its clinical features,
explore whether these families are at a higher risk of other cancers,
perform the first systematic review of the pathology of familial
testicular cancers, examine the emotional and psychosocial issues
affecting family members, develop better health care choices for
at risk individuals, and create a repository of biological specimens
to be used in various laboratory studies intended to help us learn
more about how testicular cancer develops.
Families may participate either by providing questionnaire information
and blood samples from their home communities, or they may travel
to the NIH Clinical Center for an in-person evaluation. Expenses
related to coming to the NIH, and the costs involved in participating
in the study, are covered by the study's budget.
information on the study can be found online at: http://familial-testicular-cancer.cancer.gov