Susceptibility gene for germ cell testicular cancer localised
Scientists have localised the
susceptibility gene for germ
cell testicular cancer. A multinational study whose results
were published this month
(Nature Genetics 2000;24:197200) was set up in an attempt
to establish the genetic basis of
germ cell testicular cancer,
which encompasses seminoma,
teratoma, and mixed lesions,
and makes up over 80% of testicular cancers.
Testicular germ cell tumours
are the most prevalent form of
cancer in men aged 15-40 years
in western Europe. In the past
30 years, the incidence of testicular germ cell tumour in England and Wales has increased by more than 80%. It is currently
unknown what percentage of
this tumour is caused by an
inherited genetic susceptibility,
but estimates by the authors of
the paper have put the figure as
high as 20%.
Risk factors for testicular
germ cell tumour include a history of undescended testis, testicular dysgenesis, infertility, and a previous history of such
tumours. Testicular germ cell
tumours are particularly susceptible to chemotherapy, and an
early diagnosis in people at
higher risk because of genetic
susceptibility would therefore be
beneficial.
Previous studies using polymorphisms - DNA sequences
that have been identified to demarcate the location of the
susceptibility gene - have shown that susceptibility to testicular germ cell tumour is not
inherited in an autosomal
manner. It has also been established that the risk to brothers
of patients with testicular germ
cell tumour of also developing
such a tumour is higher (eightfold) than the risk to fathers or
sons of patients (fourfold). The
scientists hypothesised a model
for X linked inheritance from
these previous relative risk
data. Subjects were recruited
through the international testicular cancer linkage consortium and were selected from
families with two or more cases
of testicular cancer.
A genome-wide linkage
study was performed. With this
form of study, it is possible to
detect the TGCT1 gene, as it
has been named, without
knowledge of its precise location in the entire genome. The
search is for the polymorphic
sequence and not the gene
itself. Analysis of the DNA of
subjects with testicular germ
cell tumour yielded results that
showed evidence of linkage on
regions of chromosome Xq,27.
Furthermore, statistical analysis showed significant evidence
for a testicular cancer germ cell
tumour susceptibility gene on
chromosome Xq,27. The
TGCT1 locus on the Xq,27
gene is associated with a higher risk of bilateral testicular
germ cell tumour. TGCT1 may
also predispose to undescended testis. Further work is
planned ultimately to isolate
TGCT1.
Nisheeth Rajpal GKT, London
studentBMJ 2000;08:45-88 March ISSN 0966-6494
