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Imaging, Diagnosis, Prognosis |
Authors' Affiliations: 1 Division of Urology and 2 Department of Pathology, Sunnybrook and Women's College Health Sciences Centre; 3 Division of Urology and Departments of 4 Pathology and 5 Medical Imaging, University Health Network; and 6 Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada
Requests for reprints: Robert K. Nam, 2075 Bayview Avenue, MG-406, Toronto, Ontario, Canada M4N 3M5. Phone: 416-480-5075; Fax: 416-480-6121; E-mail: robert.nam{at}utoronto.ca.
Purpose: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam.
Experimental Design: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostate-specific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms.
Results: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with the TT genotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1 gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer.
Conclusions: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.
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  R. K. Nam, A. Toi, L. H. Klotz, J. Trachtenberg, M. A.S. Jewett, S. Appu, D. A. Loblaw, L. Sugar, S. A. Narod, and M. W. Kattan Assessing Individual Risk for Prostate Cancer J. Clin. Oncol., August 20, 2007; 25(24): 3582 - 3588. [Abstract] [Full Text] [PDF]
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 J. M. Cunningham, S. J. Hebbring, S. K. McDonnell, M. S. Cicek, G. B. Christensen, L. Wang, S. J. Jacobsen, J. R. Cerhan, M. L. Blute, D. J. Schaid, et al. Evaluation of Genetic Variations in the Androgen and Estrogen Metabolic Pathways as Risk Factors for Sporadic and Familial Prostate Cancer Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 969 - 978. [Abstract] [Full Text] [PDF]
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 R. K. Nam, W. W. Zhang, L. H. Klotz, J. Trachtenberg, M. A.S. Jewett, J. Sweet, A. Toi, S. Teahan, V. Venkateswaran, L. Sugar, et al. Variants of the hK2 Protein Gene (KLK2) Are Associated with Serum hK2 Levels and Predict the Presence of Prostate Cancer at Biopsy. Clin. Cancer Res., November 1, 2006; 12(21): 6452 - 6458. [Abstract] [Full Text] [PDF]
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