Hereditary Prostate Cancer: A New Discovery
We have known for many years that some cancers were hereditary, e.g.
breast cancer and colon cancer. However, based upon studies from
Johns Hopkins, it is now clear that prostate cancer should also be
included in this list. With help from the first 700 patients who
underwent radical prostatectomy at Johns Hopkins, we were able to
establish a strong association between a family history of prostate
cancer and the risk for developing the disease.
Since that original observation we have identified a new variant of
prostate cancer, hereditary prostate cancer (HPC). Families with
hereditary prostate cancer are characterized by an early age at onset
of the disease and/or the presence of cancer in multiple family
members. We derived the following operational definition for such
families: 1) prostate cancer in 3 or more first degree relatives
(father or brothers) or 2 first degree relatives if both developed
the disease before the age of 55 years; or 2) prostate cancer in
3 generations, e.g. grandfather, father, son.
The mode of inheritance is characterized as autosomal dominant.
Autosomal means that it can be transmitted by either your father or
mother. Therefore, when examining your family history it is
important to ask both your father and your mother about the presence
of prostate cancer in their brothers and father. The fact that this
disease is inherited as a dominant trait means that 50% of the male
offspring in these families are at risk for developing the disease.
Because the disease is characterized by early age at onset, male
members of these families should begin screening measures
(digital rectal examination and serum PSA measurements) at age 40
rather than 50. We estimate that 88% of offspring who inherit the
gene will develop prostate cancer by age 85. We have established a
hereditary prostate cancer registry at Johns Hopkins and have
evaluated the pedigrees of over 100 patients from around the country.
We have not yet identified any strong association between prostate
cancer and other cancers in these families. This suggests that the
mutated gene may be specific for prostate cancer. DNA samples from
multiple members of 60 families with HPC have been assembled and we
are proceeding rapidly with linkage studies to identify the mutated
gene. This gene appears to be responsible for an early rate limiting
step in the development of prostate cancer. The isolation of this
gene someday will help identify affected members in HPC families.
Also, it will provide major insight into the cause of the disease and
hopefully, new approaches to prevention and treatment.
- Carter, B.S., Bova, G.S., Beaty, T.H., Steinberg, G.D,,
Childs, B., Isaacs, W.B., and Walsh, P.C.: Hereditary prostate cancer:
Epidemiologic and clinical features. J. Urol. 150:797-802, 1993.
- Carter, B.S., Beaty, T.H., Steinberg, G.D., Childs, B., and Walsh,
P.C.: Mendelian inheritance if familial prostate cancer. Proc. Natl.
Acad. Sci. 89:3367-3371, 1992.
- Steinberg, G.D., Carter, B.S., Beaty, T.H., Childs, B and Walsh,
P.C.: Family history and the risk of prostate cancer. The Prostate