Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15–40 in Western European populations1. The incidence of TGCT has risen dramatically over the last century2,3,4,5. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility6, previously diagnosed TGCT (ref. 7) and a family history of the disease8,9,10. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion 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 susceptibility gene on chromosome Xq27 that may also predispose to UDT.
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We thank the families and the clinicians, including T. Sandeman and K. Cox, for participation; J. Nicholls for collecting many of the ICR families; and E. Peacock for help in preparing the manuscript. We acknowledge the support of the Cancer Research Campaign, the New South Wales Cancer Council and the Imperial Cancer Research Fund.
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