Letter abstract


Nature Genetics 41, 811 - 815 (2009)
Published online: 31 May 2009 | doi:10.1038/ng.393

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

Peter A Kanetsky1,2, Nandita Mitra1,2, Saran Vardhanabhuti1, Mingyao Li1, David J Vaughn2,3, Richard Letrero2,4, Stephanie L Ciosek2,4, David R Doody5, Lauren M Smith4, JoEllen Weaver6, Anthony Albano7, Chu Chen5,8, Jacqueline R Starr5,8,9, Daniel J Rader10,11, Andrew K Godwin6, Muredach P Reilly10,11, Hakon Hakonarson7, Stephen M Schwartz5,8 & Katherine L Nathanson2,4

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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 times 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 times 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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  1. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  2. Abramson Cancer Center, Divisions of Hematology-Oncology and Medical Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  3. Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  4. Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  5. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  6. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
  7. Center for Applied Genomics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  8. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
  9. Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington, USA.
  10. Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  11. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Correspondence to: Katherine L Nathanson2,4 e-mail: knathans@mail.med.upenn.edu



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