Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

Gillian Crockford; Rachel Linger; Sarah Hockley; Darshna Dudakia; Lola Johnson; Robert Huddart; Kathy Tucker; Michael Friedlander; Kelly-Anne Phillips; David Hogg; Michael Jewett; Radka Lohynska; Gedske Daugaard; Stéphane Richard; Agnès Chompret; Catherine Bonaïti-Pellié; Axel Heidenreich; Peter Albers; Edith Olah; Lajos Geczi; Istvan Bodrogi; Wilma Ormiston; Peter Daly; Parry Guilford; Sophie Fosså; Ketil Heimdal; Sergei Tjulandin; Ludmila Liubchenko; Hans Stoll; Walter Weber; David Forman; Timothy Oliver; Lawrence Einhorn; Mary Mcmaster; Joan Kramer; Mark Greene; Barbara Weber; Katherine Nathanson; Victoria Cortessis; Douglas Easton; D Timothy Bishop; Michael Stratton; Elizabeth Rapley

doi:10.1093/hmg/ddi459

Journal articles

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

Gillian Crockford ¹ Rachel Linger ² Sarah Hockley ² Darshna Dudakia ² Lola Johnson ² Robert Huddart ³ Kathy Tucker ⁴ Michael Friedlander ⁴ Kelly-Anne Phillips ⁵ David Hogg ⁶ Michael Jewett ⁶ Radka Lohynska ⁷ Gedske Daugaard ⁸ Stéphane Richard ^{9, 10} Agnès Chompret ¹¹ Catherine Bonaïti-Pellié ¹² Axel Heidenreich ¹³ Peter Albers ¹⁴ Edith Olah ¹⁵ Lajos Geczi ¹⁵ Istvan Bodrogi ¹⁵ Wilma Ormiston ¹⁶ Peter Daly ¹⁶ Parry Guilford ¹⁷ Sophie Fosså ¹⁸ Ketil Heimdal ¹⁸ Sergei Tjulandin ¹⁹ Ludmila Liubchenko ¹⁹ Hans Stoll ²⁰ Walter Weber ²⁰ David Forman ²¹ Timothy Oliver ²² Lawrence Einhorn ²² Mary Mcmaster ²³ Joan Kramer ²³ Mark Greene ²³ Barbara Weber ²⁴ Katherine Nathanson ²⁴ Victoria Cortessis ²⁵ Douglas Easton ²⁶ D Timothy Bishop ¹ Michael Stratton ² Elizabeth Rapley ^{2, *}

* Corresponding author

1 Genetic Epidemiology Division, Cancer Research UK Clinical Centre

2 Section of Cancer Genetics

3 Academic Radiotherapy Unit

4 Dept of Medical Oncology, Division of Medicine

5 Dept of Haematology and Medical Oncology

6 Princess Margaret Hospital

7 Dept of Radiotherapy and Oncology

8 Dept of Oncology

9 GO - UMR 8125 - Génétique oncologique

10 Service d'urologie

11 Onco-génétique

Département de médecine oncologique [Gustave Roussy]

12 Inserm U535 - Génétique épidémiologique et structures des populations humaines

13 Dept of Urological Oncology

14 Department of Urology

15 Department of Molecular Genetics and Department of Chemotherapy

16 Department of Medical Oncology

17 Cancer Genetics Laboratory

18 Departments of Clinical Cancer Research and genetics

19 Laboratory of Clinical Genetics

20 Medical Oncology

21 Cancer Epidemiology

22 Department of Medical Oncology

23 Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics

24 Depts of Medicine and Biostatistics and Epidemology

25 Department of Preventive Medicine

26 Cancer Research U.K. Genetic Epidemiology Unit

Abstract : 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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Journal articles

Domain :

Life Sciences [q-bio] / Santé publique et épidémiologie

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Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

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Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

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