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Correspondence

Nature Genetics 40, 1032–1034 (1 September 2008) | doi:10.1038/ng0908-1032

Variation in KLK genes, prostate-specific antigen and risk of prostate cancer

Jiyoung Ahn , Sonja I Berndt , Sholom Wacholder , Peter Kraft , Adam S Kibel , Meredith Yeager , Demetrius Albanes , Edward Giovannucci , Meir J Stampfer , Jarmo Virtamo , Michael J Thun , Heather Spencer Feigelson , Geraldine Cancel-Tassin , Olivier Cussenot , Gilles Thomas , David J Hunter , Joseph F Fraumeni Jr. , Robert N Hoover , Stephen J Chanock & Richard B Hayes

To the Editor: Recently, SNPs in KLK3 were found to be related to prostate cancer risk in a genome-wide association study (GWAS; 1,854 cases) and two candidate gene investigations (596 and 209 cases, respectively), raising the possibility that KLK3 and its encoded protein PSA (prostate-specific antigen; kallikrein-related peptidase), which is widely used as a biomarker for prostate cancer detection, are etiologically related to this disease. Understanding the contribution of common genetic variation in KLK3 to prostate cancer risk is daunting, because SNPs in KLK3 are determinants of serum PSA concentrations and observed risk relationships could thus be due to differential identification of cases in settings where PSA is used in screening or clinical diagnosis of this disease.