Single nucleotide polymorphism of the human kallikrein-2 gene highly correlates with serum human kallikrein-2 levels and in combination enhances prostate cancer detection.
OBJECTIVE
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.


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.


CONCLUSIONS
The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.
Nam
Robert K
RK
Division of Urology, 2075 Bayview Ave, MG-406, Toronto, Ontario, Canada, M4N 3M5. robert.nam@utoronto.ca
Zhang
William W
WW
Trachtenberg
John
J
Diamandis
Eleftherios
E
Toi
Ants
A
Emami
Marjan
M
Ho
Minnie
M
Sweet
Joan
J
Evans
Andrew
A
Jewett
Michael A S
MA
Narod
Steven A
SA
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020840:Tissue Kallikreins / Q000097:blood* / Q000235:genetics*
D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen