Original Investigation

Human Genetics

, Volume 122, Issue 3, pp 251-259

Tagging SNPs in the kallikrein genes 3 and 2 on 19q13 and their associations with prostate cancer in men of European origin

  • Prodipto PalAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center
  • , Huifeng XiAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center
  • , Guangyun SunAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center
  • , Ritesh KaushalAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center
  • , Joshua J. MeeksAffiliated withDepartment of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University
  • , C. Shad ThaxtonAffiliated withDepartment of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University
  • , Saurav GuhaAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center
  • , Carol H. JinAffiliated withDepartment of Psychiatry, Washington University School of Medicine
  • , Brian K. SuarezAffiliated withDepartment of Psychiatry, Washington University School of Medicine
    • , William J. CatalonaAffiliated withDepartment of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University
    • , Ranjan DekaAffiliated withDepartment of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center Email author 

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Abstract

Two of the classical kallikrein genes KLK3 and KLK2 on 19q13.4 are plausible candidates in prostate cancer susceptibility. They are expressed almost exclusively in prostate tissue. We have performed a comprehensive analysis of association of variants in these two genes with prostate cancer among men of European descent using a tagging SNP approach. Thirteen SNPs selected from the HapMap database were analyzed in a sample of 596 histologically verified prostate cancer cases and 567 ethnically matched controls. Five SNPs showed significant association at single marker level. Linkage disequilibrium (LD) analysis revealed four LD blocks. We performed a haplotype analysis within each LD block. A major haplotype in block 1 that contains the first two significantly associated SNPs was significantly underrepresented in the prostate cancer cases; a second haplotype in block 3 also showed significant frequency differences between cases and controls. Four of the studied SNPs show positive associations with serum PSA levels. A structure analysis revealed no population stratification in our samples that could have confounded the association results. These findings suggest a plausible role of kallikrein gene variants in the etiology of prostate cancer among men of European ancestry.