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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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.[1]


  1. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Nathanson, K.L., Kanetsky, P.A., Hawes, R., Vaughn, D.J., Letrero, R., Tucker, K., Friedlander, M., Phillips, K.A., Hogg, D., Jewett, M.A., Lohynska, R., Daugaard, G., Richard, S., Chompret, A., Bonaïti-Pellié, C., Heidenreich, A., Olah, E., Geczi, L., Bodrogi, I., Ormiston, W.J., Daly, P.A., Oosterhuis, J.W., Gillis, A.J., Looijenga, L.H., Guilford, P., Fosså, S.D., Heimdal, K., Tjulandin, S.A., Liubchenko, L., Stoll, H., Weber, W., Rudd, M., Huddart, R., Crockford, G.P., Forman, D., Oliver, D.T., Einhorn, L., Weber, B.L., Kramer, J., McMaster, M., Greene, M.H., Pike, M., Cortessis, V., Chen, C., Schwartz, S.M., Bishop, D.T., Easton, D.F., Stratton, M.R., Rapley, E.A. Am. J. Hum. Genet. (2005) [Pubmed]
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