Testis cancer.

Abstract

Although the concept that transplacentally acting estrogen-mimicking chemicals damage fetal germ cells is still the most favored hypothesis to explain the link between declining sperm counts and rising testis cancer, there has been increasing recognition that other mechanisms may be contributing. With reports confirming the association between a sedentary lifestyle and rising incidence of testis cancer and a fourfold increased relative risk of delay in conception of more than 3 months found for those driving a vehicle for more than 3 hours a day, there is increasing recognition that heat may be one of the most important cofactors. The role of p53 in heat-mediated damage and deficiency of heat shock protein response of germ cells and germ cell cancer are providing increasing interest in the search for molecular mechanisms to explain the unique chemosensitivity of this group of tumors. Perhaps the most controversial report was the finding of mutations insufficient to block apoptosis in 67% of tumor p53 genes using a RNA-SSCP analysis, when only a quarter of them had mutations identified by conventional DNA sequencing. The acceptance that immunosuppression, whether HIV- or chemically induced, increases risk of germ cell cancer by 20 to 50 times that in the general population is perhaps the most important final confirmation of the immune-surveillance hypothesis, although there is no evidence as yet that it seriously worsens the chance of long-term cure in these patients. Further progress is being reported on the use of high-dose chemotherapy and stem-cell transplants, although the risks of treatment-related mortality still restrict its use to second line treatment. The problem of patient consent to the increasing range of options for early-stage disease is something highlighted from reports over the past year that will undoubtedly be an important issue in the future.