Human Molecular Genetics Advance Access originally published online on January 11, 2006
Human Molecular Genetics 2006 15(3):443-451; doi:10.1093/hmg/ddi459
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Genome-wide linkage screen for testicular germ cell tumour susceptibility loci
1Genetic Epidemiology Division, Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK, 2Section of Cancer Genetics, 3Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK, 4Department of Medical Oncology, Division of Medicine, University of New South Wales and Prince of Wales Hospital Randwick, Sydney Australia, 5Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia, 6Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada, 7Department of Radiotherapy and Oncology, University Hospital, Prague, Czech Republic, 8Department of Oncology, Rigshospitalet, Copenhagen, Denmark, 9Génétique Oncologique EPHE-UMR 8125 Faculté de Médecine Paris-Sud and Service d'Urologie, CHU, Le Kremlin-Bicêtre, France, 10Génétique Oncologique, Institut Gustave Roussy, Villejuif, France, 11INSERM U535, Hôpital Paul Brousse, Villejuif, France, 12Department of Urological Oncology, Phillips University, Marburg, Germany, 13Department of Urology, Klinikum Kassel GmbH, Moenchebergstr. 41-43, D-34125 Kassel, Germany, 14Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, Budapest, Hungary, 15Department of Medical Oncology, St James's Hospital, Dublin, Ireland, 16Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand, 17Departments of Clinical Cancer Research and Genetics, Rikshospitalet-Radiumhospitalet Trust, Oslo, Norway, 18Laboratory of Clinical Genetics, Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation, 19Medical Oncology, University Hospital, Basel, Switzerland, 20Cancer Epidemiology, University of Leeds, Cookridge Hospital, Leeds LS16 6QB, UK, 21Department of Medical Oncology, Barts and The London Queen Mary's School of Medicine, London, UK, 22Department of Medicine, Indiana University School of Medicine, IN, USA, 23Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health, Rockville, MD, USA, 24Departments of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 25Department of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, CA, USA and 26Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK
* To whom correspondence should be addressed at: Section of Cancer Genetics, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. Tel: +44 2087224007; Fax: +44 2087224452; Email: liz.rapley{at}icr.ac.uk
Received October 7, 2005; Accepted December 14, 2005
A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
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