Testis cancer: genes, environment, hormones.

摘要: Testicular cancer (TC) is the most common in males aged 20-40 years, with a worldwide incidence of 7.5 per 100,000, but rates vary considerably between countries and ethnic groups there evidence also for an increasing last decades. About 95% all TCs are represented by testicular germ cell tumors (TGCTs), which include seminoma non-seminoma histological types. It generally assumed that development TGCT under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity believed to represent key events progression. Furthermore, recent has suggested genetic association variations genes involved hypothalamic-pituitary-testicular axis steroidogenic enzymes. This expands current knowledge on role contribution susceptibility, supports hypothesis hormone metabolism might change hormonal environment implicated carcinogenesis. Therefore, carcinogenesis important controversial area research TGCT, further attention given factors influencing hormone-related risk. The component general strong. fact, although environmental clearly contribute (and probably its some geographical areas), proportion susceptibility accounted effects estimated at 25%. high familial risks compared other types no more than two-fold: brothers individuals have 8- 12-fold increased risk disease, sons affected 4- 6-fold Despite this strong relative risk, early results from linkage studies identified limited relationship factors, suggesting genetically complex trait. However, recently, four genome-wide (GWAS) UK USA reported TGCTs six new loci (KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP). strongest was found SNPs KITLG (ligand membrane-bound receptor tyrosine kinase KIT) gene greater 2.5-fold disease major allele, highest any date. These being now replicated researches these variations, frequently associated anomalies reproductive tract, such as cryptorchidism infertility. Finally, over past few decades, TCGT focused external causes acting mainly disrupters androgen oestrogen pathways, even during foetal testis. well known dysgenesis syndrome (TDS) hypothesis, proposed ten years ago, suggests disturbed fetal life may result one or disorders postnatally, named cryptorchidism, hypospadias, poor semen quality, TGCT. therefore considered clinical entity linked together epidemiological pathophysiological relations. genetics development, interactions disruptors another interesting research.