Monday, April 16, 2012

Genitourinary Cancer Predisposition Syndromes

Genitourinary malignancies comprise a heterogenous group of cancers of the prostate,
bladder, kidney, and testis that either, only (prostate and testis), or, more
commonly (bladder male/female ratio 3:1; kidney male/female ratio 2:1), occur in
men. Early epidemiologic studies recognized a hereditary component to all 4 cancers,
and subsequent linkage studies identified several rare syndromes whose phenotypes
include a genitourinary malignancy.

Among these 4 cancers, testicular
cancer seems to have the highest familial clustering, followed by prostate, kidney,
and then bladder cancer.
Prostate cancer is the most frequent nondermatologic malignancy in the United
States and the second commonest cause of cancer death in men, after lung cancer.
Despite evidence from segregation analyses supporting the existence of prostate
cancer susceptibility genes, few have been identified. BRCA is a rare exception that
has been consistently replicated and seems to explain 2% to 5% of familial prostate

The discovery of germline determinants of bladder cancer has been
similarly elusive. Familial bladder cancer is well recognized but its genetic cause has
not yet been explained, and associations with rare predisposition syndromes such as
Lynch syndrome (LS) or hereditary retinoblastoma (RB) explain only a minority of its
inheritance. The incidence of renal cell cancer is increasing annually, largely because
of the incidental discovery of small kidney tumors on imaging whose cause remains
poorly understood. Birt-Hogg-Dub e (BHD) syndrome, hereditary leiomyomatosisand renal cell cancer syndrome (HLRCC), von Hippel-Lindau (VHL) syndrome and
Wilms tumor-aniridia-genitourinary anomalies-mental retardation (WAGR) explain
some, but, again, a minority of hereditary kidney cancer. Testicular cancer is most
common in white men with a 75% lower incidence reported in African American
men, and, like kidney cancer, its incidence is increasing annually. The cause of this
increased incidence is unknown, but sons and brothers of affected men have a sixto
tenfold increased risk of developing testicular cancer, and family history is the strongest
risk factor for the disease, suggesting a strong genetic component.



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