The Y deletion gr/gr and susceptibility to testicular germ cell tumor

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, Agnès Chompret, Catherine Bonaïti-Pellié, Axel Heidenreich, Edith Olah, Lajos Geczi, Istvan Bodrogi, Wilma J. OrmistonPeter 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

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region-known as the "gr/gr" deletion-has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.

Original languageEnglish
Pages (from-to)1034-1043
Number of pages10
JournalAmerican Journal of Human Genetics
Volume77
Issue number6
DOIs
StatePublished - Dec 2005

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Odds Ratio
Confidence Intervals
Infertility
Testicular Germ Cell Tumor
Chromosomes, Human, Y
Seminoma
Penetrance
Male Infertility
Germ Cells
Epidemiologic Studies
Neoplasms
Alleles
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Nathanson, K. L., Kanetsky, P. A., Hawes, R., Vaughn, D. J., Letrero, R., Tucker, K., ... Rapley, E. A. (2005). The Y deletion gr/gr and susceptibility to testicular germ cell tumor. American Journal of Human Genetics, 77(6), 1034-1043. https://doi.org/10.1086/498455

The Y deletion gr/gr and susceptibility to testicular germ cell tumor. / Nathanson, Katherine L.; Kanetsky, Peter A.; Hawes, Rachel; Vaughn, David J.; Letrero, Richard; Tucker, Kathy; Friedlander, Michael; Phillips, Kelly Anne; Hogg, David; Jewett, Michael A S; Lohynska, Radka; Daugaard, Gedske; Richard, Stéphane; Chompret, Agnès; Bonaïti-Pellié, Catherine; Heidenreich, Axel; Olah, Edith; Geczi, Lajos; Bodrogi, Istvan; Ormiston, Wilma J.; Daly, Peter A.; Oosterhuis, J. Wolter; Gillis, Ad J M; Looijenga, Leendert H J; Guilford, Parry; Fosså, Sophie D.; Heimdal, Ketil; Tjulandin, Sergei A.; Liubchenko, Ludmila; Stoll, Hans; Weber, Walter; Rudd, Matthew; Huddart, Robert; Crockford, Gillian P.; Forman, David; Oliver, D. Timothy; Einhorn, Lawrence; Weber, Barbara L.; Kramer, Joan; McMaster, Mary; Greene, Mark H.; Pike, Malcolm; Cortessis, Victoria; Chen, Chu; Schwartz, Stephen M.; Bishop, D. Timothy; Easton, Douglas F.; Stratton, Michael R.; Rapley, Elizabeth A.

In: American Journal of Human Genetics, Vol. 77, No. 6, 12.2005, p. 1034-1043.

Research output: Contribution to journalArticle

Nathanson, KL, Kanetsky, PA, Hawes, R, Vaughn, DJ, Letrero, R, Tucker, K, Friedlander, M, Phillips, KA, Hogg, D, Jewett, MAS, Lohynska, R, Daugaard, G, Richard, S, Chompret, A, Bonaïti-Pellié, C, Heidenreich, A, Olah, E, Geczi, L, Bodrogi, I, Ormiston, WJ, Daly, PA, Oosterhuis, JW, Gillis, AJM, Looijenga, LHJ, Guilford, P, Fosså, SD, Heimdal, K, Tjulandin, SA, Liubchenko, L, Stoll, H, Weber, W, Rudd, M, Huddart, R, Crockford, GP, Forman, D, Oliver, DT, Einhorn, L, Weber, BL, Kramer, J, McMaster, M, Greene, MH, Pike, M, Cortessis, V, Chen, C, Schwartz, SM, Bishop, DT, Easton, DF, Stratton, MR & Rapley, EA 2005, 'The Y deletion gr/gr and susceptibility to testicular germ cell tumor', American Journal of Human Genetics, vol. 77, no. 6, pp. 1034-1043. https://doi.org/10.1086/498455
Nathanson KL, Kanetsky PA, Hawes R, Vaughn DJ, Letrero R, Tucker K et al. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. American Journal of Human Genetics. 2005 Dec;77(6):1034-1043. https://doi.org/10.1086/498455
Nathanson, Katherine L. ; Kanetsky, Peter A. ; Hawes, Rachel ; Vaughn, David J. ; Letrero, Richard ; Tucker, Kathy ; Friedlander, Michael ; Phillips, Kelly Anne ; Hogg, David ; Jewett, Michael A S ; Lohynska, Radka ; Daugaard, Gedske ; Richard, Stéphane ; Chompret, Agnès ; Bonaïti-Pellié, Catherine ; Heidenreich, Axel ; Olah, Edith ; Geczi, Lajos ; Bodrogi, Istvan ; Ormiston, Wilma J. ; Daly, Peter A. ; Oosterhuis, J. Wolter ; Gillis, Ad J M ; Looijenga, Leendert H J ; Guilford, Parry ; Fosså, Sophie D. ; Heimdal, Ketil ; Tjulandin, Sergei A. ; Liubchenko, Ludmila ; Stoll, Hans ; Weber, Walter ; Rudd, Matthew ; Huddart, Robert ; Crockford, Gillian P. ; Forman, David ; Oliver, D. Timothy ; Einhorn, Lawrence ; Weber, Barbara L. ; Kramer, Joan ; McMaster, Mary ; Greene, Mark H. ; Pike, Malcolm ; Cortessis, Victoria ; Chen, Chu ; Schwartz, Stephen M. ; Bishop, D. Timothy ; Easton, Douglas F. ; Stratton, Michael R. ; Rapley, Elizabeth A. / The Y deletion gr/gr and susceptibility to testicular germ cell tumor. In: American Journal of Human Genetics. 2005 ; Vol. 77, No. 6. pp. 1034-1043.
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T1 - The Y deletion gr/gr and susceptibility to testicular germ cell tumor

AU - Nathanson, Katherine L.

AU - Kanetsky, Peter A.

AU - Hawes, Rachel

AU - Vaughn, David J.

AU - Letrero, Richard

AU - Tucker, Kathy

AU - Friedlander, Michael

AU - Phillips, Kelly Anne

AU - Hogg, David

AU - Jewett, Michael A S

AU - Lohynska, Radka

AU - Daugaard, Gedske

AU - Richard, Stéphane

AU - Chompret, Agnès

AU - Bonaïti-Pellié, Catherine

AU - Heidenreich, Axel

AU - Olah, Edith

AU - Geczi, Lajos

AU - Bodrogi, Istvan

AU - Ormiston, Wilma J.

AU - Daly, Peter A.

AU - Oosterhuis, J. Wolter

AU - Gillis, Ad J M

AU - Looijenga, Leendert H J

AU - Guilford, Parry

AU - Fosså, Sophie D.

AU - Heimdal, Ketil

AU - Tjulandin, Sergei A.

AU - Liubchenko, Ludmila

AU - Stoll, Hans

AU - Weber, Walter

AU - Rudd, Matthew

AU - Huddart, Robert

AU - Crockford, Gillian P.

AU - Forman, David

AU - Oliver, D. Timothy

AU - Einhorn, Lawrence

AU - Weber, Barbara L.

AU - Kramer, Joan

AU - McMaster, Mary

AU - Greene, Mark H.

AU - Pike, Malcolm

AU - Cortessis, Victoria

AU - Chen, Chu

AU - Schwartz, Stephen M.

AU - Bishop, D. Timothy

AU - Easton, Douglas F.

AU - Stratton, Michael R.

AU - Rapley, Elizabeth A.

PY - 2005/12

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