Objectives: To clarify the association of kallikrein-related peptidase 3 (KLK3) rs2735839 G/A polymorphism with serum prostate-specific antigen (PSA) levels in Japanese men. Methods: Subjects were participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study who visited the Seirei Preventive Health Care Center in Shizuoka, Japan. Among the 5,040 individuals aged 35–69 years who were enrolled in 2006–2007, serum PSA data were available for 2,323 male subjects without a past history of prostate cancer. The diagnostic criteria for PSA positivity was PSA ≥4.0 ng/ml. Genotyping of the KLK3 polymorphism was conducted by the polymerase chain reaction with the confronting two-pair primers (PCR-CTPP) method. Results: The mean ± SD of PSA levels (mg/dl) were 1.54 ± 1.73 for those with KLK3 rs2735839 G/G genotype, 1.34 ± 1.33 for G/A, and 1.20 ± 1.23 for A/A, which was significantly different (p < 0.0001). The age-adjusted odds ratios of PSA test positivity were 0.62 (95% confidence interval 0.41–0.94) for those with G/A + A/A relative to those with G/G. Conclusions: The present study revealed that the KLK3 rs2735839 G allele was significantly associated with higher serum PSA levels also in Japanese.

Keywords:
Prostate-specific antigen, Kallikrein-related peptidase 3, Prostate cancer, Single nucleotide polymorphism
1.
Nakata S, Takahashi H, Ohtake N, Takei T, Yamanaka H: Trends and characteristics in prostate cancer mortality in Japan. Int J Urol 2000;7:254–257.
2.
Loeb S, Catalona WJ: Prostate-specific antigen screening: pro. Curr Opin Urol 2010;20:185–188.
3.
Gudmundsson J, Besenbacher S, Sulem P, et al: Genetic correction of PSA values using sequence variants associated with PSA levels. Sci Transl Med 2010;2:62ra92.
4.
Gsur A, Preyer M, Haidinger G, et al: Polymorphic CAG repeats in the androgen receptor gene, prostate-specific antigen polymorphism and prostate cancer risk. Carcinogenesis 2002;23:1647–1651.
5.
Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK: Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 2008;40:316–321.
6.
Hamajima N, J-MICC Study Group: The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer. Asian Pac J Cancer Prev 2007;8:317–323.
7.
Asai Y, Naito M, Suzuki M, et al: Baseline data of Shizuoka area in the Japan Multi-institutional Collaborative Cohort Study (J-MICC Study). Nagoya J Med Sci 2009;71:137–144.
8.
Tokudome S, Goto C, Imaeda N, Tokudome Y, Ikeda M, Maki S: Development of a data-based short food frequency questionnaire for assessing nutrient intake by middle-aged Japanese. Asian Pac J Cancer Prev 2004;5:40–43.
9.
Tokudome Y, Goto C, Imaeda N, et al: Relative validity of a short food frequency questionnaire for assessing nutrient intake versus three-day weighed diet records in middle-aged Japanese. J Epidemiol 2005;15:135–145.
10.
Goto C, Tokudome Y, Imaeda N, et al: Validation study of fatty acid consumption assessed with a short food frequency questionnaire against plasma concentration in middle-aged Japanese people. Scand J Nutr 2006;50:77–82.
11.
Imaeda N, Goto C, Tokudome Y, Hirose K, Tajima K, Tokudome S: Reproducibility of a short food frequency questionnaire for Japanese general population. J Epidemiol 2007;17:100–107.
12.
Hamajima N, Saito T, Matsuo K, Kozaki K, Takahashi T, Tajima K: Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res 2000;91:865–868.
13.
Xu J, Isaacs SD, Sun J, et al: Association of prostate cancer risk variants with clinicopathologic characteristics of the disease. Clin Cancer Res 2008;14:5819–5824.
14.
Hulka BS, Grimson RC, Greenberg BG, et al: ‘Alternate’ controls in a case-control study of endometrial cancer and exogenous estrogen. Am J Epidemiol 1980;112:376–387.
15.
Grover VK, Cole DE, Hamilton DC: Attributing Hardy-Weinberg disequilibrium to population stratification and genetic association in case-control studies. Ann Hum Genet 2010;74:77–87.
16.
Ando R, Nagaya T, Hashimoto Y, et al: Inverse relationship between obesity and serum prostate-specific antigen level in healthy Japanese men: a hospital-based cross-sectional survey, 2004–2006. Urology 2008;72:561–565.
17.
Culp S, Porter M: The effect of obesity and lower serum prostate-specific antigen levels on prostate-cancer screening results in American men. BJU Int 2009;104:1457–1461.
18.
Blouin K, Veilleux A, Luu-The V, Tchernof A: Androgen metabolism in adipose tissue: Recent advances. Mol Cell Endocrinol 2009;301:97–103.
19.
Kupelian V, Hayes FJ, Link CL, Rosen R, McKinlay JB: Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab 2008;93:3403–3410.
20.
Habuchi T, Liqing Z, Suzuki T, et al: Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect. Cancer Res 2000;60:5710–5713.
21.
Lewis SJ, Murad A, Chen L, et al: Associations between an obesity-related genetic variant (FTO rs9939609) and prostate cancer risk. PLoS One 2010;5:e13485.
22.
Whitaker HC, Kote-Jarai Z, Ross-Adams H, et al: The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine. PLoS One 2010;5:e13363.
23.
Yeager M, Orr N, Hayes RB, et al: Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 2007;39:645–649.
24.
Gudmundsson J, Sulem P, Manolescu A, et al: Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 2007;39:631–637.
25.
Freedman ML, Haiman CA, Patterson N, et al: Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 2006;103:14068–14073.
26.
Eeles RA, Kote-Jarai Z, Al Olama AA, et al: Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet 2009;41:1116–1121.
27.
Ahn J, Berndt SI, Wacholder S, et al: Variation in KLK genes, prostate-specific antigen and risk of prostate cancer. Nat Genet 2008;40:1032–1034.
28.
Pal P, Xi H, Sun G, et al: Tagging SNPs in the kallikrein genes 3 and 2 on 19q13 and their associations with prostate cancer in men of European origin. Hum Genet 2007;122:251–259.
29.
Lindstrom S, Schumacher F, Siddiq A, et al: Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers – results from BPC3. PLoS One 2011;6:e17142.
30.
Gallagher DJ, Vijai J, Cronin AM, et al: Susceptibility loci associated with prostate cancer progression and mortality. Clin Cancer Res 2010;16:2819–2832.
31.
Pampalakis G, Sotiropoulou G: Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer. Biochim Biophys Acta 2007;1776:22–31.
32.
Database of Single Nucleotide Polymorphisms (dbSNP) homepage (http://www.ncbi.nlm.nih.gov/snp).
33.
Takata R, Akamatsu S, Kubo M, et al: Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat Genet 2010;42:751–754.
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2012
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