Testicular germ cell tumors (TGCTs) affect 1 in 500 men and are the most common cancer in males aged 15 to 40 in western European populations. The incidence of TGCT rose dramatically during the 20th century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT, and a family history of the disease. Brothers of men with TGCT have an 8- to 10-fold risk of developing TGCT, whereas the relative risk to fathers and sons is 4-fold. This familial relative risk is much higher than that for most other types of cancer (summary by Rapley et al., 2000). Genetic Heterogeneity of Testicular Germ Cell Tumors A locus for testicular germ cell tumors (TGCT1; 300228) has been identified on chromosome Xq27.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers. Five cancer types account for the majority of LFS tumors: adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas. Other cancers associated with LFS include leukemia, colorectal cancer, stomach cancer, lung cancer, melanoma, pediatric head and neck cancers, pancreatic cancer, and prostate cancer. Cancer survivors are at increased risk for developing additional primary cancers and treatment-related secondary cancers. The lifetime risks of cancer for women and men with classic LFS are 90% and 70%, respectively, and 50% of cancers occur prior to age 40 years.