Nature Genetics
24, 197 - 200 (2000)
doi:10.1038/72877
Localization to Xq27 of a susceptibility gene for testicular germ-cell tumoursElizabeth A. Rapley1, Gillian P. Crockford2, Dawn Teare3, Patrick Biggs1, Sheila Seal1, Rita Barfoot1, Sandra Edwards1, Rifat Hamoudi1, Ketil Heimdal4, Sophie D. Fosså5, Kathy Tucker6, Jenny Donald7, Felicity Collins6, Michael Friedlander6, David Hogg8, Paul Goss8, Axel Heidenreich9, Wilma Ormiston10, Peter A. Daly10, David Forman2, Timothy D. Oliver2, Michael Leahy2, Robert Huddart1, Colin S. Cooper1, Julia G. Bodmer11, Douglas F. Easton3, Michael R. Stratton1
& D. Timothy Bishop21
Sections of Cancer Genetics and Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK. 2
Imperial Cancer Research Fund Genetic Epidemiology Lab, Ashley Wing, Leeds, UK. 3
CRC Genetic Epidemiology Unit, Strangeways Research Laboratories, Worts Causeway, Cambridge, UK. 4
Unit of Medical Genetics, Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway. 5
Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway. 6
Department of Oncology, Prince of Wales Hospital, Randwick, Australia. 7
Department of Biological Sciences, Macquarie University, N.S.W., Australia. 8
Department of Medicine, University of Toronto, Medical Sciences Building, Ontario, Canada. 9
Department of Urology, Philipps-University, Marburg, Germany. 10
Department of Medical Oncology, Hope Directorate, St James's Hospital, Dublin, Ireland. 11
Imperial Cancer Research Fund, Cancer Genetics & Immunology Laboratory, John Radcliffe Hospital, Oxford, UK.
Correspondence should be addressed to Michael R. Stratton mikes@icr.ac.ukTesticular 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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