Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours

Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most co mmon cancer in males aged 15-40 in Western European populations(1). The inc idence of TGCT has risen dramatically over the last century(2-5) Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility(6), previously diagnosed TGCT (ref. 7) and a famil y history of the disease(8-10). Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers a nd sons is fourfold (ref. 9). This familial relative risk is much higher th an that for most other types of cancer. We have collected samples from 134 families with two or mom cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity Iod (hIod) score of 2. 01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hIod score of 4.7 from families with at least one bilateral case , corresponding to a genome-wide significance level of P=0.034. The proport ion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susc eptibility gene on chromosome Xq27 that may also predispose to UDT.