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Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23
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Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23 HUMAN MOLECULAR GENETICS Schumacher, F. R., Wang, Z., Skotheim, R. I., Koster, R., Chung, C. C., Hildebrandt, M. A., Kratz, C. P., Bakken, A. C., Bishop, D. T., Cook, M. B., Erickson, R. L., Fossa, S. D., Greene, M. H., Jacobs, K. B., Kanetsky, P. A., Kolonel, L. N., Loud, J. T., Korde, L. A., Le Marchand, L., Lewinger, J. P., Lothe, R. A., Pike, M. C., Rahman, N., Rubertone, M. V., Schwartz, S. M., Siegmund, K. D., Skinner, E. C., Turnbull, C., Van den Berg, D. J., Wu, X., Yeager, M., Nathanson, K. L., Chanock, S. J., Cortessis, V. K., McGlynn, K. A. 2013; 22 (13): 2748-2753Abstract
Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.
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