PURPOSE: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk. PATIENTS AND METHODS: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively. RESULTS: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P =.0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P =.004) and 1.51 (95% CI, 1.2 to 2.0; P =.002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P =.0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P =.0001) for patients with high hK2 levels and at least one T allele. CONCLUSION: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.
PURPOSE: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the humankallikrein-2 gene (KLK2), circulating humankallikrein-2 (hK2) levels and prostate cancer risk. PATIENTS AND METHODS: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively. RESULTS: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P =.0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P =.004) and 1.51 (95% CI, 1.2 to 2.0; P =.002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P =.0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P =.0001) for patients with high hK2 levels and at least one T allele. CONCLUSION: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.
Authors: Roberto A Lleras; Leslie R Adrien; Richard V Smith; Benjamin Brown; Naheed Jivraj; Christopher Keller; Cathy Sarta; Nicolas F Schlecht; Thomas M Harris; Geoffrey Childs; Michael B Prystowsky; Thomas J Belbin Journal: Am J Pathol Date: 2011-05 Impact factor: 4.307
Authors: Robert J Klein; Christer Halldén; Angel M Cronin; Alexander Ploner; Fredrik Wiklund; Anders S Bjartell; Pär Stattin; Jianfeng Xu; Peter T Scardino; Kenneth Offit; Andrew J Vickers; Henrik Grönberg; Hans Lilja Journal: Cancer Prev Res (Phila) Date: 2010-04-27
Authors: Andrew J Vickers; Angel M Cronin; Monique J Roobol; Caroline J Savage; Mari Peltola; Kim Pettersson; Peter T Scardino; Fritz H Schröder; Hans Lilja Journal: Clin Cancer Res Date: 2010-04-16 Impact factor: 12.531
Authors: 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; Robert N Hoover; Stephen J Chanock; Richard B Hayes Journal: Nat Genet Date: 2008-09 Impact factor: 38.330