The genetics of testicular germ cell tumours

Testicular Germ Cell Tumours (TGCT) affect 1 in 400 men in the UK. Two per cent of TGCT cases report another affected family member. The familial relative risk is estimated to be 8-10 fold for brothers of cases and 4-6 fold for fathers and sons. This familial relative risk is considerably higher than for most common cancers suggesting that the contribution of genetic factors to TGCT may be relatively more important than for other cancers. However, the search by genetic linkage analysis for familial TGCT susceptibility genes has been confounded by the limited number of large multiple case families. The International Testicular Cancer Linkage Consortium family set currently consists of more than 190 families with at least two cases of TGCT. A genome-wide search conducted on 100 families has yielded strong evidence for a TGCT susceptibility gene on the X chromosome. This gene appears to predispose to bilateral TGCT and also possibly to undescended testis. This is the first familial TGCT gene to be localised and the first cancer susceptibility gene mapped in a genome wide search using predominantly sib pairs.