Atrophy, hormones, genes and viruses in aetiology germ cell tumours.

This chapter reviews the evidence that testicular germ cell atrophy could be the final common pathway for all of the established and postulated risk factors for induction of testis tumours. The evidence from age incidence studies shows that the tumour peak incidence follows the curve of sexual activity in the male, and this provides the starting point for the argument that this tumour is dependent on endocrine factors for its induction. The data from epidemiological studies confirming the high frequency of atrophogenic events and occurrence of low sperm counts in more than 75% of patients provide the principal evidence in support of this hypothesis. The need for more information on hormone sensitivity of this group of tumours and in particular the more differentiated variety, ie seminoma, is highlighted. Information on levels of DNA repair enzyme activity as an explanation of radiosensitivity and chemosensitivity of this group of tumours is also needed. The relationship of HLA linked immune response genes to susceptibility to testicular atrophogenic virus infection needs further investigation, particularly in view of the recent introduction of widespread prepubertal vaccination against mumps virus, one of the most clearly identified testicular atrophogenic viruses. The paper concludes with an examination of the influence of carcinogens and radiation and how they relate to modern ideas of clonal evolution of tumours. The conclusion from this review is that testicular germ cell tumours provide an excellent model of the recent postulate of Ames et al, (1990) that for some cancers mitogenesis might precede mutagenesis, in contrast to the classical view produced from animal models that mutagenic induction is followed by mitogenic promotion.