Literature DB >> 19483682

Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer.

Peter A Kanetsky1, Nandita Mitra, Saran Vardhanabhuti, Mingyao Li, David J Vaughn, Richard Letrero, Stephanie L Ciosek, David R Doody, Lauren M Smith, Joellen Weaver, Anthony Albano, Chu Chen, Jacqueline R Starr, Daniel J Rader, Andrew K Godwin, Muredach P Reilly, Hakon Hakonarson, Stephen M Schwartz, Katherine L Nathanson.   

Abstract

Testicular germ cell tumors (TGCT) have been expected to have a strong underlying genetic component. We conducted a genome-wide scan among 277 TGCT cases and 919 controls and found that seven markers at 12p22 within KITLG (c-KIT ligand) reached genome-wide significance (P < 5.0 x 10(-8) in discovery). In independent replication, TGCT risk was increased threefold per copy of the major allele at rs3782179 and rs4474514 (OR = 3.08, 95% CI = 2.29-4.13; OR = 3.07, 95% CI = 2.29-4.13, respectively). We found associations with rs4324715 and rs6897876 at 5q31.3 near SPRY4 (sprouty 4; P < 5.0 x 10(-6) in discovery). In independent replication, risk of TGCT was increased nearly 40% per copy of the major allele (OR = 1.37, 95% CI = 1.14-1.64; OR = 1.39, 95% CI = 1.16-1.66, respectively). All of the genotypes were associated with both seminoma and nonseminoma TGCT subtypes. These results demonstrate that common genetic variants affect TGCT risk and implicate KITLG and SPRY4 as genes involved in TGCT susceptibility.

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Year:  2009        PMID: 19483682      PMCID: PMC2865677          DOI: 10.1038/ng.393

Source DB:  PubMed          Journal:  Nat Genet        ISSN: 1061-4036            Impact factor:   38.330


  29 in total

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Authors:  Katherine L Nathanson; Peter A Kanetsky; Rachel Hawes; David J Vaughn; Richard Letrero; Kathy Tucker; Michael Friedlander; Kelly-Anne Phillips; David Hogg; Michael A S Jewett; Radka Lohynska; Gedske Daugaard; Stéphane Richard; Agnés Chompret; Catherine Bonaïti-Pellié; Axel Heidenreich; Edith Olah; Lajos Geczi; Istvan Bodrogi; Wilma J Ormiston; Peter A Daly; J Wolter Oosterhuis; Ad J M Gillis; Leendert H J Looijenga; Parry Guilford; Sophie D Fosså; Ketil Heimdal; Sergei A Tjulandin; Ludmila Liubchenko; Hans Stoll; Walter Weber; Matthew Rudd; Robert Huddart; Gillian P Crockford; David Forman; D Timothy Oliver; Lawrence Einhorn; Barbara L Weber; Joan Kramer; Mary McMaster; Mark H Greene; Malcolm Pike; Victoria Cortessis; Chu Chen; Stephen M Schwartz; D Timothy Bishop; Douglas F Easton; Michael R Stratton; Elizabeth A Rapley
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Journal:  Cell       Date:  2007-12-14       Impact factor: 41.582

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  151 in total

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Review 5.  Transgenerational genetic effects on phenotypic variation and disease risk.

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Review 6.  [Genetics of testicular germ cell tumors].

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9.  Incidence of testicular germ cell tumors among US men by census region.

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