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A haplotype at chromosome Xq27.2 confers susceptibility to prostate cancer

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Abstract

We conducted an association study to identify risk variants for familial prostate cancer within the HPCX locus at Xq27 among Americans of Northern European descent. We investigated a total of 507 familial prostate cancer probands and 507 age-matched controls without a personal or family history of prostate cancer. The study population was subdivided into a set of training subjects to explore genetic variation of the locus potentially impacting risk of prostate cancer, and an independent set of test subjects to confirm the association and to assign significance, addressing multiple comparisons. We identified a 22.9 kb haplotype nominally associated with prostate cancer among training subjects (292 cases, 292 controls; χ2 = 5.08, P = 0.020), that was confirmed among test subjects (215 cases, 215 controls; χ2 = 3.73, P = 0.040). The haplotype predisposed to prostate cancer with an odds ratio of 3.41 (95% CI 1.04–11.17, P = 0.034) among test subjects. The haplotype extending from rs5907859 to rs1493189 is concordant with a prior study of the region within the Finnish founder population, and warrants further independent investigation.

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Acknowledgments

We extend particular thanks to the study participants and to Drs Joseph Smith, Michael Cookson, Sam Chang, Richard Hock, William Maynard, Jason Pereira, and William Dupont. This work was supported by an award from the V Foundation, by a MERIT grant from the US Department of Veterans Affairs, by grant W81XWH-06-1-0057 from the Department of the Army, and by General Clinical Research Center grant M01 RR-00095 from the National Center for Research Resources, National Institutes of Health.

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Authors and Affiliations

  1. Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Brian L. Yaspan & Jeffrey R. Smith

  2. Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 529 Light Hall, 2215 Garland Avenue, Nashville, TN, 37232-0275, USA

    Kate M. McReynolds, J. Bradford Elmore, Joan P. Breyer, Kevin M. Bradley & Jeffrey R. Smith

  3. Medical Research Service, VA Tennessee Valley Healthcare System, Nashville, TN, USA

    Jeffrey R. Smith

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  1. Brian L. Yaspan
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  2. Kate M. McReynolds
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  3. J. Bradford Elmore
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Correspondence to Jeffrey R. Smith.

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Yaspan, B.L., McReynolds, K.M., Elmore, J.B. et al. A haplotype at chromosome Xq27.2 confers susceptibility to prostate cancer. Hum Genet 123, 379–386 (2008). https://doi.org/10.1007/s00439-008-0486-8

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