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A Novel Prostate Cancer Susceptibility Locus at 19q13

Centers for ¹ Cancer Genomics and ² Human Genomics and ³ Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; ⁵ Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland; ⁶ Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden; and ⁷ Translational Genomics Research Institute, Phoenix, Arizona

Requests for reprints: William B. Isaacs, Marburg 115, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287. Phone: 410-955-2518; Fax: 410-955-0833; E-mail: wisaacs{at}jhmi.edu.

Key Words: prostate cancer • association • genetic • 19q13

A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P < 0.05). We then genotyped these two SNPs in the remaining cases (n = 2,393) and controls (n = 1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P = 9.4 x 10^–4). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P = 3.2 x 10^–7 from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted. [Cancer Res 2009;69(7):2720–3]